Honors & Awards

  • ACS Nano Junior Fellow, ACS Nano/Kavli Foundation (2017)
  • Herman Lopata Memorial Hepatitis Postdoctoral Research Fellowship Award, American Liver Foundation (2016)
  • MSE Doctorate Technopreneur Award, Nanyang Technological University (2016)
  • Grand Prize Award, Nano Korea Symposium (2013)
  • Nanyang President’s Graduate Scholar, Nanyang Technological University (2011-2015)
  • Martinos Scholar, Harvard-MIT Division of Health Sciences and Technology (2011)
  • Department of Chemistry Crow Award, University of Florida (2010)
  • Graduate Research Fellowship (Bioengineering), National Science Foundation (2010)
  • MEMP Graduate Fellowship, Harvard-MIT Division of Health Sciences and Technology (2010)
  • SURE Fellowship, NSF Center for Polymer Interfaces and Macromolecular Assemblies (CPIMA) (2009)
  • Extramural Research Award, UF-HHMI Science for Life (2008)
  • Phi Beta Kappa, University of Florida (2008)
  • Beckman Scholars Fellowship, Arnold and Mabel Beckman Foundation (2007)
  • John V. Lombardi Scholarship, University of Florida (2006)
  • Robert C. Byrd Honors Scholarship, U.S. Department of Education (2006)

Professional Education

  • Doctor of Philosophy, Nanyang Technological University (2015)
  • Bachelor of Science, University of Florida (2010)

Stanford Advisors

All Publications

  • Co-assembly of Peptide Amphiphiles and Lipids into Supramolecular Nanostructures Driven by Anion-p Interactions. Journal of the American Chemical Society Yu, Z., Erbas, A., Tantakitti, F., Palmer, L. C., Jackman, J. A., Olvera de la Cruz, M., Cho, N., Stupp, S. I. 2017


    Co-assembly of binary systems driven by specific non-covalent interactions can greatly expand the structural and functional space of supramolecular nanostructures. We report here on the self-assembly of peptide amphiphiles and fatty acids driven primarily by anion-π interactions. The peptide sequences investigated were functionalized with a perfluorinated phenylalanine residue to promote anion-π interactions with carboxylate headgroups in fatty acids. These interactions were verified here by NMR and circular dichroism experiments as well as investigated using atomistic simulations. Positioning the aromatic units close to the N-terminus of the peptide backbone near the hydrophobic core of cylindrical nanofibers leads to strong anion-π interactions between both components. With a low content of dodecanoic acid in this position, the cylindrical morphology is preserved. However, as the aromatic units are moved along the peptide backbone away from the hydrophobic core, the interactions with dodecanoic acid transform the cylindrical supramolecular morphology into ribbon-like structures. Increasing the ratio of dodecanoic acid to PA leads to either the formation of large vesicles in the binary systems where the anion-π interactions are strong, or a heterogeneous mixture of assemblies when the peptide amphiphiles associate weakly with dodecanoic acid. Our findings reveal how co-assembly involving designed specific interactions can drastically change supramolecular morphology and even cross from nano to micro scales.

    View details for DOI 10.1021/jacs.7b02058

    View details for PubMedID 28571316

  • Optimizing the Formation of Supported Lipid Bilayers from Bicellar Mixtures. Langmuir Kolahdouzan, K., Jackman, J. A., Yoon, B. K., Kim, M. C., Johal, M. S., Cho, N. 2017; 33 (20): 5052-5064


    Supported lipid bilayers (SLBs) are widely studied model membrane platforms that are compatible with various surface-sensitive measurement techniques. SLBs are typically formed on silica-based materials, and there are numerous possible fabrication routes involving either bottom-up molecular self-assembly or vesicle adsorption and rupture. In between these two classes of fabrication strategies lies an emerging approach based on depositing quasi-two-dimensional lamellar, bicellar disks composed of a mixture of long-chain and short-chain phospholipids to promote the formation of SLBs. This approach takes advantage of the thermodynamic preference of long-chain phospholipids to form planar SLBs, whereas short-chain phospholipids have brief residence times. Although a few studies have shown that SLBs can be formed on silica-based materials from bicellar mixtures, outstanding questions remain about the self-assembly mechanism as well as the influence of the total phospholipid concentration, ratio of the two phospholipids (termed the "q-ratio"), and process of sample preparation. Herein, we address these questions through comprehensive quartz crystal microbalance-dissipation, fluorescence microscopy, and fluorescence recovery after photobleaching experiments. Our findings identify that optimal SLB formation occurs at lower total concentrations of phospholipids than previously used as short-chain phospholipids behave like membrane-destabilizing detergents at higher concentrations. Using lower phospholipid concentrations, we also discovered that the formation of SLBs proceeds through a two-step mechanism involving a critical coverage of bicellar disks akin to vesicle fusion. In addition, the results indicate that at least one cycle of freeze-thaw-vortexing is useful during the sample preparation process to produce SLBs. Taken together, the findings in this work identify optimal routes for fabricating SLBs from bicellar mixtures and reveal mechanistic details about the bicelle-mediated SLB formation process, which will aid further exploration of bicellar mixtures as tools for model membrane fabrication.

    View details for DOI 10.1021/acs.langmuir.7b00210

    View details for PubMedID 28457139

  • Nanoplasmonic sensors for biointerfacial science. Chemical Society reviews Jackman, J. A., Rahim Ferhan, A., Cho, N. 2017


    In recent years, nanoplasmonic sensors have become widely used for the label-free detection of biomolecules across medical, biotechnology, and environmental science applications. To date, many nanoplasmonic sensing strategies have been developed with outstanding measurement capabilities, enabling detection down to the single-molecule level. One of the most promising directions has been surface-based nanoplasmonic sensors, and the potential of such technologies is still emerging. Going beyond detection, surface-based nanoplasmonic sensors open the door to enhanced, quantitative measurement capabilities across the biointerfacial sciences by taking advantage of high surface sensitivity that pairs well with the size of medically important biomacromolecules and biological particulates such as viruses and exosomes. The goal of this review is to introduce the latest advances in nanoplasmonic sensors for the biointerfacial sciences, including ongoing development of nanoparticle and nanohole arrays for exploring different classes of biomacromolecules interacting at solid-liquid interfaces. The measurement principles for nanoplasmonic sensors based on utilizing the localized surface plasmon resonance (LSPR) and extraordinary optical transmission (EOT) phenomena are first introduced. The following sections are then categorized around different themes within the biointerfacial sciences, specifically protein binding and conformational changes, lipid membrane fabrication, membrane-protein interactions, exosome and virus detection and analysis, and probing nucleic acid conformations and binding interactions. Across these themes, we discuss the growing trend to utilize nanoplasmonic sensors for advanced measurement capabilities, including positional sensing, biomacromolecular conformation analysis, and real-time kinetic monitoring of complex biological interactions. Altogether, these advances highlight the rich potential of nanoplasmonic sensors and the future growth prospects of the community as a whole. With ongoing development of commercial nanoplasmonic sensors and analytical models to interpret corresponding measurement data in the context of biologically relevant interactions, there is significant opportunity to utilize nanoplasmonic sensing strategies for not only fundamental biointerfacial science, but also translational science applications related to clinical medicine and pharmaceutical drug development among countless possibilities.

    View details for DOI 10.1039/c6cs00494f

    View details for PubMedID 28383083

  • Quantitative Profiling of Nanoscale Liposome Deformation by a Localized Surface Plasmon Resonance Sensor ANALYTICAL CHEMISTRY Jackman, J. A., Avsar, S. Y., Ferhan, A. R., Li, D., Park, J. H., Zhdanov, V. P., Cho, N. 2017; 89 (2): 1102-1109


    Characterizing the shape of sub-100 nm, biological soft-matter particulates (e.g., liposomes and exosomes) adsorbed at a solid-liquid interface remains a challenging task. Here, we introduce a localized surface plasmon resonance (LSPR) sensing approach to quantitatively profile the deformation of nanoscale, fluid-phase 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes contacting a titanium dioxide substrate. Experimental and theoretical results validate that, due to its high sensitivity to the spatial proximity of phospholipid molecules near the sensor surface, the LSPR sensor can discriminate fine differences in the extent of ionic strength-modulated liposome deformation at both low and high surface coverages. By contrast, quartz crystal microbalance-dissipation (QCM-D) measurements performed with equivalent samples were qualitatively sensitive to liposome deformation only at saturation coverage. Control experiments with stiffer, gel-phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes verified that the LSPR measurement discrimination arises from the extent of liposome deformation, while the QCM-D measurements yield a more complex response that is also sensitive to the motion of adsorbed liposomes and coupled solvent along with lateral interactions between liposomes. Collectively, our findings demonstrate the unique measurement capabilities of LSPR sensors in the area of biological surface science, including competitive advantages for probing the shape properties of adsorbed, nanoscale biological particulates.

    View details for DOI 10.1021/acs.analchem.6b02532

    View details for Web of Science ID 000392458100013

    View details for PubMedID 27983791

  • Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H ACS NANO Belling, J. N., Jackman, J. A., Avsar, S. Y., Park, J. H., Wang, Y., Potroz, M. G., Ferhan, A. R., Weiss, P. S., Cho, N. 2016; 10 (11): 10161-10172


    With mounting evidence that nanomaterials can trigger adverse innate immune responses such as complement activation, there is increasing attention to the development of strategies that mask the complement-activating properties of nanomaterials. The current gold standard to reduce complement activation of nanomaterials is the covalent attachment of polymer coatings on nanomaterial surfaces, even though this strategy provides only moderate protection against complement activation. Akin to protein coronas that form on nanomaterial surfaces in physiological fluids, noncovalent strategies based on protein adsorption would offer a simplified, biomimetic approach to mitigate complement activation. Herein, we demonstrate that precoating graphene-based nanomaterials with purified, natural proteins enables regulatory control of nanomaterial-triggered complement activation. When the graphene-based nanomaterials were coated with complement factor H, nearly complete protection (>90% reduction) against complement activation (a "stealth effect") was achieved. By contrast, coating the nanomaterials with a passivating layer of bovine or human serum albumins achieved moderate protection (∼40% reduction), whereas immunoglobulin G amplified complement activation by several-fold. Taken together, our results demonstrate that surface-bound factor H, as well as serum albumins, can prevent graphene oxide-triggered complement activation, thereby offering a facile approach to inhibit complement activation completely down to naturally occurring levels.

    View details for DOI 10.1021/acsnano.6b05409

    View details for Web of Science ID 000388913100045

    View details for PubMedID 27792317

  • Influence of Divalent Cations on Deformation and Rupture of Adsorbed Lipid Vesicles LANGMUIR Dacic, M., Jackman, J. A., Yorulmaz, S., Zhdanov, V. P., Kasemo, B., Cho, N. 2016; 32 (25): 6486-6495


    The fate of adsorbed lipid vesicles on solid supports depends on numerous experimental parameters and typically results in the formation of a supported lipid bilayer (SLB) or an adsorbed vesicle layer. One of the poorly understood questions relates to how divalent cations appear to promote SLB formation in some cases. The complexity arises from the multiple ways in which divalent cations affect vesicle-substrate and vesicle-vesicle interactions as well as vesicle properties. These interactions are reflected, e.g., in the degree of deformation of adsorbed vesicles (if they do not rupture). It is, however, experimentally challenging to measure the extent of vesicle deformation in real-time. Herein, we investigated the effect of divalent cations (Mg(2+), Ca(2+), Sr(2+)) on the adsorption of zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid vesicles onto silicon oxide- and titanium oxide-coated substrates. The vesicle adsorption process was tracked using the quartz crystal microbalance-dissipation (QCM-D) and localized surface plasmon resonance (LSPR) measurement techniques. On silicon oxide, vesicle adsorption led to SLB formation in all cases, while vesicles adsorbed but did not rupture on titanium oxide. It was identified that divalent cations promote increased deformation of adsorbed vesicles on both substrates and enhanced rupture on silicon oxide in the order Ca(2+) > Mg(2+) > Sr(2+). The influence of divalent cations on different factors in these systems is discussed, clarifying experimental observations on both substrates. Taken together, the findings in this work offer insight into how divalent cations modulate the interfacial science of supported membrane systems.

    View details for DOI 10.1021/acs.langmuir.6b00439

    View details for Web of Science ID 000378973300029

    View details for PubMedID 27182843

  • Inflated Sporopollenin Exine Capsules Obtained from Thin-Walled Pollen SCIENTIFIC REPORTS Park, J. H., Seo, J., Jackman, J. A., Cho, N. 2016; 6


    Sporopollenin is a physically robust and chemically resilient biopolymer that comprises the outermost layer of pollen walls and is the first line of defense against harsh environmental conditions. The unique physicochemical properties of sporopollenin increasingly motivate the extraction of sporopollenin exine capsules (SECs) from pollen walls as a renewable source of organic microcapsules for encapsulation applications. Despite the wide range of different pollen species with varying sizes and wall thicknesses, faithful extraction of pollen-mimetic SECs has been limited to thick-walled pollen capsules with rigid mechanical properties. There is an unmet need to develop methods for producing SECs from thin-walled pollen capsules which constitute a large fraction of all pollen species and have attractive materials properties such as greater aerosol dispersion. Herein, we report the first successful extraction of inflated SEC microcapsules from a thin-walled pollen species (Zea mays), thereby overcoming traditional challenges with mechanical stability and loss of microstructure. Morphological and compositional characterization of the SECs obtained by the newly developed extraction protocol confirms successful protein removal along with preservation of nanoscale architectural features. Looking forward, there is excellent potential to apply similar strategies across a wide range of unexplored thin-walled pollen species.

    View details for DOI 10.1038/srep28017

    View details for Web of Science ID 000384561400001

    View details for PubMedID 27302853

  • Correlating single-molecule and ensemble-average measurements of peptide adsorption onto different inorganic materials PHYSICAL CHEMISTRY CHEMICAL PHYSICS Kim, S., Jackman, J. A., Mochizuki, M., Yoon, B. K., Hayashi, T., Cho, N. 2016; 18 (21): 14454-14459


    The coating of solid-binding peptides (SBPs) on inorganic material surfaces holds significant potential for improved surface functionalization at nano-bio interfaces. In most related studies, the goal has been to engineer peptides with selective and high binding affinity for a target material. The role of the material substrate itself in modulating the adsorption behavior of a peptide molecule remains less explored and there are few studies that compare the interaction of one peptide with different inorganic substrates. Herein, using a combination of two experimental techniques, we investigated the adsorption of a 16 amino acid-long random coil peptide to various inorganic substrates - gold, silicon oxide, titanium oxide and aluminum oxide. Quartz crystal microbalance-dissipation (QCM-D) experiments were performed in order to measure the peptide binding affinity for inorganic solid supports at the ensemble average level, and atomic force microscopy (AFM) experiments were conducted in order to determine the adhesion force of a single peptide molecule. A positive trend was observed between the total mass uptake of attached peptide and the single-molecule adhesion force on each substrate. Peptide affinity for gold was appreciably greater than for the oxide substrates. Collectively, the results obtained in this study offer insight into the ways in which inorganic materials can differentially influence and modulate the adhesion of SBPs.

    View details for DOI 10.1039/c6cp01168c

    View details for Web of Science ID 000378102700039

    View details for PubMedID 27174015

  • Nanotechnology Education for the Global World: Training the Leaders of Tomorrow ACS NANO Jackman, J. A., Cho, D., Lee, J., Chen, J. M., Besenbacher, F., Bonnell, D. A., Hersam, M. C., Weiss, P. S., Cho, N. 2016; 10 (6): 5595-5599


    Nanoscience is one of the fastest growing and most impactful fields in global scientific research. In order to support the continued development of nanoscience and nanotechnology, it is important that nanoscience education be a top priority to accelerate research excellence. In this Nano Focus, we discuss current approaches to nanoscience training and propose a learning design framework to promote the next generation of nanoscientists. Prominent among these are the abilities to communicate and to work across and between conventional disciplines. While the United States has played leading roles in initiating these developments, the global landscape of nanoscience calls for worldwide attention to this educational need. Recent developments in emerging nanoscience nations are also discussed. Photo credit: Jae Hyeon Park.

    View details for DOI 10.1021/acsnano.6b03872

    View details for Web of Science ID 000378973700002

    View details for PubMedID 27310728

  • High-performance 3D printing of hydrogels by water-dispersible photoinitiator nanoparticles. Science advances Pawar, A. A., Saada, G., Cooperstein, I., Larush, L., Jackman, J. A., Tabaei, S. R., Cho, N., Magdassi, S. 2016; 2 (4)


    In the absence of water-soluble photoinitiators with high absorbance in the ultraviolet (UV)-visible range, rapid three-dimensional (3D) printing of hydrogels for tissue engineering is challenging. A new approach enabling rapid 3D printing of hydrogels in aqueous solutions is presented on the basis of UV-curable inks containing nanoparticles of highly efficient but water-insoluble photoinitiators. The extinction coefficient of the new water-dispersible nanoparticles of 2,4,6-trimethylbenzoyl-diphenylphosphine oxide (TPO) is more than 300 times larger than the best and most used commercially available water-soluble photoinitiator. The TPO nanoparticles absorb significantly in the range from 385 to 420 nm, making them suitable for use in commercially available, low-cost, light-emitting diode-based 3D printers using digital light processing. The polymerization rate at this range is very fast and enables 3D printing that otherwise is impossible to perform without adding solvents. The TPO nanoparticles were prepared by rapid conversion of volatile microemulsions into water-dispersible powder, a process that can be used for a variety of photoinitiators. Such water-dispersible photoinitiator nanoparticles open many opportunities to enable rapid 3D printing of structures prepared in aqueous solutions while bringing environmental advantages by using low-energy curing systems and avoiding the need for solvents.

    View details for DOI 10.1126/sciadv.1501381

    View details for PubMedID 27051877

  • Plasmonic Nanohole Sensor for Capturing Single Virus-Like Particles toward Virucidal Drug Evaluation SMALL Jackman, J. A., Linardy, E., Yoo, D., Seo, J., Ng, W. B., Klemme, D. J., Wittenberg, N. J., Oh, S., Cho, N. 2016; 12 (9): 1159-1166


    A plasmonic nanohole sensor for virus-like particle capture and virucidal drug evaluation is reported. Using a materials-selective surface functionalization scheme, passive immobilization of virus-like particles only within the nanoholes is achieved. The findings demonstrate that a low surface coverage of particles only inside the functionalized nanoholes significantly improves nanoplasmonic sensing performance over conventional nanohole arrays.

    View details for DOI 10.1002/smll.201501914

    View details for Web of Science ID 000372008600007

    View details for PubMedID 26450658

  • Nanomedicine for Infectious Disease Applications: Innovation towards Broad-Spectrum Treatment of Viral Infections SMALL Jackman, J. A., Lee, J., Cho, N. 2016; 12 (9): 1133-1139


    Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation.

    View details for DOI 10.1002/smll.201500854

    View details for Web of Science ID 000372008600003

    View details for PubMedID 26551316

  • Deciphering How Pore Formation Causes Strain-Induced Membrane Lysis of Lipid Vesicles JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Jackman, J. A., Goh, H. Z., Zhdanov, V. P., Knoll, W., Cho, N. 2016; 138 (4): 1406-1413


    Pore formation by membrane-active antimicrobial peptides is a classic strategy of pathogen inactivation through disruption of membrane biochemical gradients. It remains unknown why some membrane-active peptides also inhibit enveloped viruses, which do not depend on biochemical gradients. Here, we employ a label-free biosensing approach based on simultaneous quartz crystal microbalance-dissipation and ellipsometry measurements in order to investigate how a pore-forming, virucidal peptide destabilizes lipid vesicles in a surface-based experimental configuration. A key advantage of the approach is that it enables direct kinetic measurement of the surface-bound peptide-to-lipid (P:L) ratio. Comprehensive experiments involving different bulk peptide concentrations and biologically relevant membrane compositions support a unified model that membrane lysis occurs at or above a critical P:L ratio, which is at least several-fold greater than the value corresponding to the onset of pore formation. That is consistent with peptide-induced pores causing additional membrane strain that leads to lysis of highly curved membranes. Collectively, the work presents a new model that describes how peptide-induced pores may destabilize lipid membranes through a membrane strain-related lytic process, and this knowledge has important implications for the design and application of membrane-active peptides.

    View details for DOI 10.1021/jacs.5b12491

    View details for Web of Science ID 000369558000046

    View details for PubMedID 26751083

  • Relationship between vesicle size and steric hindrance influences vesicle rupture on solid supports PHYSICAL CHEMISTRY CHEMICAL PHYSICS Jackman, J. A., Kim, M. C., Zhdanov, V. P., Cho, N. 2016; 18 (4): 3065-3072


    Phospholipid assemblies on solid supports mimic the cell membrane, and provide a platform to study membrane biology. Among the different types of model membranes, the planar bilayer is a two-dimensional lipid bilayer sheet that can be formed by the adsorption and spontaneous rupture of vesicles. The formation process is influenced by the interactions between vesicles and the solid support as well as between vesicles. On silicon oxide, which is a commonly used solid support, vesicles typically adsorb until reaching a critical coverage and then spontaneous rupture begins. Although it is generally understood that spontaneous rupture leads to planar bilayer formation, oversaturation of vesicles at the critical coverage can hinder the whole process due to a steric factor. To date, the role of this factor has been scrutinized only in relation to temperature, and the influence of additional parameters remains to be elucidated. In this work, we have investigated how vesicle size and corresponding steric constraints influence the kinetics of vesicle adsorption and rupture and, more specifically, how the state of adsorbed vesicles after fusion depends on the vesicle size. Using quartz crystal microbalance-dissipation (QCM-D) and fluorescence recovery after photobleaching (FRAP), we characterized the adsorption kinetics of vesicles onto silicon oxide and the lateral mobility of solid-supported lipid assemblies. While the vesicle adsorption kinetics were diffusion-limited up to the onset of vesicle rupture, the extent of rupture depended on vesicle size and it was observed that larger vesicles are more prone to steric effects than smaller vesicles. We discuss this finding in terms of the structural transformation from adsorbed vesicles to a planar bilayer, including how the interplay of thermodynamic, kinetic and steric factors can affect vesicle rupture on solid supports.

    View details for DOI 10.1039/c5cp06786c

    View details for Web of Science ID 000369506000085

    View details for PubMedID 26739602

  • Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide BIOPHYSICAL JOURNAL Hanson, J. M., Gettel, D. L., Tabaei, S. R., Jackman, J., Kim, M. C., Sasaki, D. Y., Groves, J. T., Liedberg, B., Cho, N., Parikh, A. N. 2016; 110 (1): 176-187


    The α-helical (AH) domain of the hepatitis C virus nonstructural protein NS5A, anchored at the cytoplasmic leaflet of the endoplasmic reticulum, plays a role in viral replication. However, the peptides derived from this domain also exhibit remarkably broad-spectrum virocidal activity, raising questions about their modes of membrane association. Here, using giant lipid vesicles, we show that the AH peptide discriminates between membrane compositions. In cholesterol-containing membranes, peptide binding induces microdomain formation. By contrast, cholesterol-depleted membranes undergo global softening at elevated peptide concentrations. Furthermore, in mixed populations, the presence of ∼100 nm vesicles of viral dimensions suppresses these peptide-induced perturbations in giant unilamellar vesicles, suggesting size-dependent membrane association. These synergistic composition- and size-dependent interactions explain, in part, how the AH domain might on the one hand segregate molecules needed for viral assembly and on the other hand furnish peptides that exhibit broad-spectrum virocidal activity.

    View details for DOI 10.1016/j.bpj.2015.11.032

    View details for Web of Science ID 000367783900010

    View details for PubMedID 26745420

  • Nanoplasmonic ruler to measure lipid vesicle deformation. Chemical communications Jackman, J. A., Špacková, B., Linardy, E., Kim, M. C., Yoon, B. K., Homola, J., Cho, N. 2016; 52 (1): 76-79


    A nanoplasmonic ruler method is presented in order to measure the deformation of adsorbed, nm-scale lipid vesicles on solid supports. It is demonstrated that single adsorbed vesicles undergo greater deformation on silicon oxide over titanium oxide, offering direct experimental evidence to support membrane tension-based theoretical models of supported lipid bilayer formation.

    View details for DOI 10.1039/c5cc06861d

    View details for PubMedID 26466086

  • Comparison of Complement Activation-Related Pseudoallergy in Miniature and Domestic Pigs: Foundation of a Validatable Immune Toxicity Model Nanomedicine: Nanotechnology, Biology and Medicine Jackman, J. A., Mészáros , T., Fülöp , T., Urbanics, R., Szebeni, J., Cho, N. 2016; 12 (4): 933–943
  • Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides Molecules Jackman, J. A., Yoon, B., Li, D., Cho, N. 2016; 21 (3)
  • Nanotechnology Education for the Global World: Training the Leaders of Tomorrow ACS Nano Jackman, J. A., Cho, D., Lee, J., Chen, J., Besenbacher, F., Bonnell, D. A., Hersam, M. C., Weiss, P. S., Cho, N. 2016; 10 (6): 5595-5599

    View details for DOI 10.1021/acsnano.6b03872

  • Inflated Sporopollenin Exine Capsules Obtained from Thin-Walled Pollen Scientific Reports Park, J., Seo, J., Jackman, J. A., Cho, N. 2016; 6

    View details for DOI 10.1038/srep28017

  • Nanoplasmonic ruler to measure lipid vesicle deformation CHEMICAL COMMUNICATIONS Jackman, J. A., Spackova, B., Linardy, E., Kim, M. C., Yoon, B. K., Homola, J., Cho, N. 2016; 52 (1): 76-79

    View details for DOI 10.1039/c5cc06861d

    View details for Web of Science ID 000366856900008

  • Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides. Molecules Jackman, J. A., Yoon, B. K., Li, D., Cho, N. 2016; 21 (3)


    Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fatty acids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fatty acids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed.

    View details for DOI 10.3390/molecules21030305

    View details for PubMedID 26950108

  • Flexible, Graphene-Coated Biocomposite for Highly Sensitive, Real-Time Molecular Detection Advanced Functional Materials Wang, L., Jackman, J. A., Ng, W., Cho, N. 2016
  • Correlating single-molecule and ensemble-average measurements of peptide adsorption onto different inorganic materials Physical Chemistry Chemical Physics Kim, S., Jackman, J. A., Mochizuki, M., Yoon, B., Hayashi, T., Cho, N. 2016; 18 (21): 14454-14459
  • Multifunctional hydrogel nano-probes for atomic force microscopy Nature Communications Lee, J., Song, J., Kim, S., Lee, W., Jackman, J. A., Kim, D., Cho, N., Lee, J. 2016; 7

    View details for DOI 10.1038/ncomms11566

  • Graphene‐Functionalized Natural Microcapsules: Modular Building Blocks for Ultrahigh Sensitivity Bioelectronic Platforms Advanced Functional Materials Wang, L., Ng, W., Jackman, J. A., Cho, N. 2016; 26 (13): 2097–2103

    View details for DOI 10.1002/adfm.201504940

  • Influence of Divalent Cations on Deformation and Rupture of Adsorbed Lipid Vesicles Langmuir Dacic, M., Jackman, J. A., Yorulmaz, S., Zhdanov, V. P., Kasemo, B., Cho, N. 2016; 32 (25): 6486–6495
  • Biomembrane Fabrication by the Solvent-assisted Lipid Bilayer (SALB) Method JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Tabaei, S. R., Jackman, J. A., Kim, M., Yorulmaz, S., Vafaei, S., Cho, N. 2015

    View details for DOI 10.3791/53073

    View details for Web of Science ID 000368574400010

  • Supported Lipid Bilayer Platform To Test Inhibitors of the Membrane Attack Complex: Insights into Biomacromolecular Assembly and Regulation BIOMACROMOLECULES Yorulmaz, S., Jackman, J. A., Hunziker, W., Cho, N. 2015; 16 (11): 3594-3602


    Complement activation plays an important role in innate immune defense by triggering formation of the membrane attack complex (MAC), which is a biomacromolecular assembly that exhibits membrane-lytic activity against foreign invaders including various pathogens and biomaterials. Understanding the details of MAC structure and function has been the subject of extensive work involving bulk liposome and erythrocyte assays. However, it is difficult to characterize the mechanism of action of MAC inhibitor drug candidates using the conventional assays. To address this issue, we employ a biomimetic supported lipid bilayer platform to investigate how two MAC inhibitors, vitronectin and clusterin, interfere with MAC assembly in a sequential addition format, as monitored by the quartz crystal microbalance-dissipation (QCM-D) technique. Two experimental strategies based on modular assembly were selected, precincubation of inhibitor and C5b-7 complex before addition to the lipid bilayer or initial addition of inhibitor followed by the C5b-7 complex. The findings indicate that vitronectin inhibits membrane association of C5b-7 via a direct interaction with C5b-7 and via competitive membrane association onto the supported lipid bilayer. On the other hand, clusterin directly interacts with C5b-7 such that C5b-7 is still able to bind to the lipid bilayer, and clusterin affects the subsequent binding of other complement proteins involved in the MAC assembly. Taken together, the findings in this study outline a biomimetic approach based on supported lipid bilayers to explore the interactions between complement proteins and inhibitors, thereby offering insight into MAC assembly and regulation.

    View details for DOI 10.1021/acs.biomac.5b01060

    View details for Web of Science ID 000364614300019

    View details for PubMedID 26444518

  • Spectrum of Membrane Morphological Responses to Antibacterial Fatty Acids and Related Surfactants. Langmuir Yoon, B. K., Jackman, J. A., Kim, M. C., Cho, N. 2015; 31 (37): 10223-10232


    Medium-chain saturated fatty acids and related compounds (e.g., monoglycerides) represent one class of membrane-active surfactants with antimicrobial properties. Most related studies have been in vitro evaluations of bacterial growth inhibition, and there is limited knowledge about how the compounds in this class destabilize lipid bilayers, which are the purported target within the bacterial cell membrane. Herein, the interaction between three representative compounds in this class and a supported lipid bilayer platform was investigated using quartz crystal microbalance-dissipation and fluorescence microscopy in order to examine membrane destabilization. The three tested compounds were lauric acid, sodium dodecyl sulfate, and glycerol monolaurate. For each compound, we discovered striking differences in the resulting morphological changes of supported lipid bilayers. The experimental trends indicate that the compounds have membrane-disruptive behavior against supported lipid bilayers principally above the respective critical micelle concentration values. The growth inhibition properties of the compounds against standard and methicillin-resistant Staphylococcus aureus bacterial strains were also tested. Taken together, the findings in this work improve our knowledge about how saturated fatty acids and related compounds destabilize lipid bilayers, offering insight into the corresponding molecular mechanisms that lead to membrane morphological responses.

    View details for DOI 10.1021/acs.langmuir.5b02088

    View details for PubMedID 26325618

  • Quantitative Evaluation of Peptide-Material Interactions by a Force Mapping Method: Guidelines for Surface Modification LANGMUIR Mochizuki, M., Oguchi, M., Kim, S., Jackman, J. A., Ogawa, T., Lkhamsuren, G., Cho, N., Hayashi, T. 2015; 31 (29): 8006-8012


    Peptide coatings on material surfaces have demonstrated wide application across materials science and biotechnology, facilitating the development of nanobio interfaces through surface modification. A guiding motivation in the field is to engineer peptides with a high and selective binding affinity to target materials. Herein, we introduce a quantitative force mapping method in order to evaluate the binding affinity of peptides to various hydrophilic oxide materials by atomic force microscopy (AFM). Statistical analysis of adhesion forces and probabilities obtained on substrates with a materials contrast enabled us to simultaneously compare the peptide binding affinity to different materials. On the basis of the experimental results and corresponding theoretical analysis, we discuss the role of various interfacial forces in modulating the strength of peptide attachment to hydrophilic oxide solid supports as well as to gold. The results emphasize the precision and robustness of our approach to evaluating the adhesion strength of peptides to solid supports, thereby offering guidelines to improve the design and fabrication of peptide-coated materials.

    View details for DOI 10.1021/acs.langmuir.5b01691

    View details for Web of Science ID 000358822300013

    View details for PubMedID 26125092

  • Correlation between Membrane Partitioning and Functional Activity in a Single Lipid Vesicle Assay Establishes Design Guidelines for Antiviral Peptides SMALL Jackman, J. A., Saravanan, R., Zhang, Y., Tabaei, S. R., Cho, N. 2015; 11 (20): 2372-2379


    The nanometer-scale discrimination of virus-rupturing peptides is tested using lipid membrane platforms. In combination with single-vesicle analysis of peptide-induced vesicle rupture, a correlation between membrane partitioning and biologically relevant activities is established. Taken together, the findings support that the degree of rupture activity should be balanced by membrane curvature-selectivity for optimal therapeutic properties of antiviral peptides.

    View details for DOI 10.1002/smll.201403638

    View details for Web of Science ID 000354827100003

    View details for PubMedID 25619175

  • Strategies for enhancing the sensitivity of plasmonic nanosensors NANO TODAY Guo, L., Jackman, J. A., Yang, H., Chen, P., Cho, N., Kim, D. 2015; 10 (2): 213-239
  • Solvent-Assisted Lipid Self-Assembly at Hydrophilic Surfaces: Factors Influencing the Formation of Supported Membranes LANGMUIR Tabaei, S. R., Jackman, J. A., Kim, S., Zhdanov, V. P., Cho, N. 2015; 31 (10): 3125-3134


    As a simple and efficient technique, the solvent-assisted lipid bilayer (SALB) formation method offers a versatile approach to fabricating a planar lipid bilayer on solid supports. Corresponding mechanistic aspects and the role of various governing parameters remain, however, to be better understood. Herein, we first scrutinized the effect of lipid concentration (0.01 to 5 mg/mL) and solvent type (isopropanol, n-propanol, or ethanol) on SALB formation on silicon oxide in order to identify optimal conditions for this process. The obtained fluid-phase lipid layers on silicon oxide were investigated by using the quartz crystal microbalance with dissipation monitoring, epifluorescence microscopy, and atomic force microscopy. The experimental results indicate that, in alcohol, lipid attachment to the substrate is reversible and reaches equilibrium in accordance with the bulk lipid concentration. During the solvent-exchange step, the water fraction increases and the deposited lipids are converted into planar bilayer fragments, along with the concurrent adsorption and rupture of micelles within an optimal lipid concentration range. In addition, fluid-phase lipid bilayers were successfully formed on other substrates (e.g., chrome, indium tin oxide, and titanium oxide) that are largely intractable to conventional methods (e.g., vesicle fusion). Moreover, gel-phase lipid bilayers were fabricated as well. Depending on the phase state of the lipid bilayer during fabrication, the corresponding adlayer mass varied by approximately 20% between the fluid- and gel-phase states in a manner which is consistent with the molecular packing of lipids in the two arrangements. Taken together, our findings help to explain the mechanistic details of SALB formation, optimize the corresponding procedure, and demonstrate the general utility for fabricating gel- and fluid-phase planar lipid bilayers.

    View details for DOI 10.1021/la5048497

    View details for Web of Science ID 000351327300023

    View details for PubMedID 25679066

  • Contribution of Temperature to Deformation of Adsorbed Vesicles Studied by Nanoplasmonic Biosensing LANGMUIR Oh, E., Jackman, J. A., Yorulmaz, S., Zhdanov, V. P., Lee, H., Cho, N. 2015; 31 (2): 771-781


    With increasing temperature, biological macromolecules and nanometer-sized aggregates typically undergo complex and poorly understood reconfigurations, especially in the adsorbed state. Herein, we demonstrate the strong potential of using localized surface plasmon resonance (LSPR) sensors to address challenging questions related to this topic. By employing an LSPR-based gold nanodisk array platform, we have studied the adsorption of sub-100-nm diameter 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid vesicles on titanium oxide at two temperatures, 23 and 50 °C. Inside this temperature range, DPPC lipid vesicles undergo the gel-to-fluid phase transition accompanied by membrane area expansion, while DOPC lipid vesicles remain in the fluid-phase state. To interpret the corresponding measurement results, we have derived general equations describing the effect of deformation of adsorbed vesicles on the LSPR signal. At the two temperatures, the shape of adsorbed DPPC lipid vesicles on titanium oxide remains nearly equivalent, while DOPC lipid vesicles become less deformed at higher temperature. Adsorption and rupture of DPPC lipid vesicles on silicon oxide were also studied for comparison. In contrast to the results obtained on titanium oxide, adsorbed vesicles on silicon oxide become more deformed at higher temperature. Collectively, the findings demonstrate that increasing temperature may ultimately promote, hinder, or have negligible effect on the deformation of adsorbed vesicles. The physics behind these observations is discussed, and helps to clarify the interplay of various, often hidden, factors involved in adsorption of biological macromolecules at interfaces.

    View details for DOI 10.1021/la504267g

    View details for Web of Science ID 000348333700015

    View details for PubMedID 25531903

  • Self-Assembly Formation of Lipid Bilayer Coatings on Bare Aluminum Oxide: Overcoming the Force of Interfacial Water ACS APPLIED MATERIALS & INTERFACES Jackman, J. A., Tabaei, S. R., Zhao, Z., Yorulmaz, S., Cho, N. 2015; 7 (1): 959-968


    Widely used in catalysis and biosensing applications, aluminum oxide has become popular for surface functionalization with biological macromolecules, including lipid bilayer coatings. However, it is difficult to form supported lipid bilayers on aluminum oxide, and current methods require covalent surface modification, which masks the interfacial properties of aluminum oxide, and/or complex fabrication techniques with specific conditions. Herein, we addressed this issue by identifying simple and robust strategies to form fluidic lipid bilayers on aluminum oxide. The fabrication of a single lipid bilayer coating was achieved by two methods, vesicle fusion under acidic conditions and solvent-assisted lipid bilayer (SALB) formation under near-physiological pH conditions. Importantly, quartz crystal microbalance with dissipation (QCM-D) monitoring measurements determined that the hydration layer of a supported lipid bilayer on aluminum oxide is appreciably thicker than that of a bilayer on silicon oxide. Fluorescence recovery after photobleaching (FRAP) analysis indicated that the diffusion coefficient of lateral lipid mobility was up to 3-fold greater on silicon oxide than on aluminum oxide. In spite of this hydrodynamic coupling, the diffusion coefficient on aluminum oxide, but not silicon oxide, was sensitive to the ionic strength condition. Extended-DLVO model calculations estimated the thermodynamics of lipid-substrate interactions on aluminum oxide and silicon oxide, and predict that the range of the repulsive hydration force is greater on aluminum oxide, which in turn leads to an increased equilibrium separation distance. Hence, while a strong hydration force likely contributes to the difficulty of bilayer fabrication on aluminum oxide, it also confers advantages by stabilizing lipid bilayers with thicker hydration layers due to confined interfacial water. Such knowledge provides the basis for improved surface functionalization strategies on aluminum oxide, underscoring the practical importance of surface hydration.

    View details for DOI 10.1021/am507651h

    View details for Web of Science ID 000348085200115

    View details for PubMedID 25513828

  • Observation of Stripe Superstructure in the beta-Two-Phase Coexistence Region of Cholesterol-Phospholipid Mixtures in Supported Membranes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Tabaei, S. R., Jackman, J. A., Liedberg, B., Parikh, A. N., Cho, N. 2014; 136 (49): 16962-16965


    Visualization of phase coexistence in the β region of cholesterol-phospholipid mixtures consisting of high cholesterol concentrations has proved elusive in lipid bilayers. Here, using the solvent-assisted lipid bilayer approach to prepare supported membranes with high cholesterol fractions close to the cholesterol solubility limit, we report the observation of coexisting liquid phases using fluorescence microscopy. At ∼63 mol % cholesterol, supported membranes consisting of mixtures of DOPC and cholesterol exhibit large-area striping reminiscent of the stripe superstructures that characterize the proximity of the second critical point in the miscibility phase diagram. The properties of the two phases are consistent with condensed complex-rich and cholesterol-rich liquids. Both phases exhibit long-range lateral mobility, and diffusion through a given phase is favored over hopping across the phase boundary, producing an "archipelago effect" and a complex percolation path.

    View details for DOI 10.1021/ja5082537

    View details for Web of Science ID 000346544200004

    View details for PubMedID 25401991

  • Controlling Lipid Membrane Architecture for Tunable Nanoplasmonic Biosensing SMALL Zan, G. H., Jackman, J. A., Kim, S., Cho, N. 2014; 10 (23): 4828-4832


    Tunable nanoplasmonic biosensing for lipid and protein applications is reported based on controlling lipid membrane architecture on surfaces. The interaction of a peptide with lipid membranes is highly sensitive to the membrane architecture on top of plasmonic nanodisks, and the measurement response varies in a manner which is consistent with the surrounding lipid environment.

    View details for DOI 10.1002/smll.201400518

    View details for Web of Science ID 000345973300002

    View details for PubMedID 25079046

  • Formation of Cholesterol-Rich Supported Membranes Using Solvent-Assisted Lipid Self-Assembly LANGMUIR Tabaei, S. R., Jackman, J. A., Kim, S., Liedberg, B., Knoll, W., Parikh, A. N., Cho, N. 2014; 30 (44): 13345-13352


    This paper describes the application of a solvent-exchange method to prepare supported membranes containing high fractions of cholesterol (up to ∼57 mol %) in an apparent equilibrium. The method exploits the phenomenon of reverse-phase evaporation, in which the deposition of lipids in alcohol (e.g., isopropanol) is followed by the slow removal of the organic solvent from the water-alcohol mixture. This in turn induces a series of lyotropic phase transitions successively producing inverse-micelles, monomers, micelles, and vesicles in equilibrium with supported bilayers at the contacting solid surface. By using the standard cholesterol depletion by methyl-β-cyclodextrin treatment, a quartz crystal microbalance with dissipation monitoring assay confirms that the cholesterol concentration in the supported membranes is comparable to that in the surrounding bulk phase. A quantitative characterization of the biophysical properties of the resultant bilayer, including lateral diffusion constants and phase separation, using epifluorescence microscopy and atomic force microscopy establishes the formation of laterally contiguous supported lipid bilayers, which break into a characteristic domain-pattern of coexisting phases in a cholesterol concentration-dependent manner. With increasing cholesterol fraction in the supported bilayer, the size of the domains increases, ultimately yielding two-dimensional cholesterol bilayer domains near the solubility limit. A unique feature of the approach is that it enables preparation of supported membranes containing limiting concentrations of cholesterol near the solubility limit under equilibrium conditions, which cannot be obtained using conventional techniques (i.e., vesicle fusion).

    View details for DOI 10.1021/ja5034433

    View details for Web of Science ID 000344905100026

    View details for PubMedID 25286344

  • Nanoplasmonic Biosensing for Soft Matter Adsorption: Kinetics of Lipid Vesicle Attachment and Shape Deformation LANGMUIR Jackman, J. A., Zhdanov, V. P., Cho, N. 2014; 30 (31): 9494-9503


    An indirect nanoplasmonic sensing platform is reported for investigating the kinetics of attachment and shape deformation associated with lipid vesicle adsorption onto a titanium oxide-coated substrate. The localized surface plasmon resonance (LSPR) originates from embedded gold nanodisks and is highly sensitive to the local lipid environment. To interpret the corresponding results, we have extended treatments of diffusion-limited adsorption kinetics and adsorbate-related LSPR physics, identified the expected scaling laws for the LSPR-tracked kinetics measured at different lipid concentrations and/or nanometer-scale vesicle sizes in the case when vesicle deformation is negligible, and scrutinized experimental deviations accordingly. After adsorption, the smallest 58 nm diameter vesicles were found to maintain shape on the time scale of adsorption at high lipid concentrations in solution, and shape deformation became more appreciable at lower lipid concentrations. Higher saturation coverage was observed with increasing lipid concentration, which is attributed to the difference in relative time scales of vesicle attachment and deformation. For larger vesicles between 80 and 160 nm diameter, deviations associated with their shape deformation and correlations with the location of gold nanodisks became more apparent at moderate and high coverages. Taken together, the results obtained support that the quantitative measurement capabilities of nanoplasmonic biosensing should be considered for applications demanding highly surface-sensitive characterization of soft matter adsorption and related phenomena at liquid-solid interfaces.

    View details for DOI 10.1021/la502431x

    View details for Web of Science ID 000340347300031

    View details for PubMedID 25035920

  • Contribution of the Hydration Force to Vesicle Adhesion on Titanium Oxide LANGMUIR Jackman, J. A., Zan, G. H., Zhao, Z., Cho, N. 2014; 30 (19): 5368-5372


    Titanium oxide is a biocompatible material that supports vesicle adhesion. Depending on experimental parameters, adsorbed vesicles remain intact or rupture spontaneously. Vesicle rupture has been attributed to electrostatic attraction between vesicles and titanium oxide, although the relative contribution of various interfacial forces remains to be clarified. Herein, we investigated the influence of vesicle surface charge on vesicle adsorption onto titanium oxide and observed that electrostatic attraction is insufficient for vesicle rupture. Following this line of evidence, a continuum model based on the DLVO forces and a non-DLVO hydration force was applied to investigate the role of different interfacial forces in modulating the lipid-substrate interaction. Within an experimentally significant range of conditions, the model shows that the magnitude of the repulsive hydration force strongly influences the behavior of adsorbed vesicles, thereby supporting that the hydration force makes a strong contribution to the fate of adsorbed vesicles on titanium oxide. The findings are consistent with literature reports concerning phospholipid assemblies on solid supports and nanoparticles and underscore the importance of the hydration force in influencing the behavior of phospholipid films on hydrophilic surfaces.

    View details for DOI 10.1021/la404581d

    View details for Web of Science ID 000336414500002

    View details for PubMedID 24796732

  • AH Peptide-Mediated Formation of Charged Planar Lipid Bilayers JOURNAL OF PHYSICAL CHEMISTRY B Zan, G. H., Jackman, J. A., Cho, N. 2014; 118 (13): 3616-3621


    Planar lipid bilayers on solid supports provide a controllable platform to mimic biological membranes. Adsorption and spontaneous rupture of vesicles is the most common method to form planar bilayers. While many substrates support vesicle adsorption, vesicles rupture spontaneously on only a few materials. In order to form planar bilayers on materials intractable to conventional vesicle fusion, an amphipathic, α-helical (AH) peptide has been identified that can rupture adsorbed vesicles and form planar bilayers on previously intractable materials. Most studies using AH peptide have employed zwitterionic lipid compositions only, and the range of suitable lipid compositions remains to be elucidated. Herein, using quartz crystal microbalance-dissipation and ellipsometry, we investigated the effects of membrane surface charge on AH peptide-mediated bilayer formation via the rupture of surface-adsorbed vesicles on titanium oxide. Our findings demonstrate that AH peptide can promote the formation of positively and negatively charged bilayers. Importantly, the kinetics of vesicle rupture by AH peptide are strongly influenced by the membrane surface charge. Although the titanium oxide surface is negatively charged, the formation of negatively charged bilayers was quickest among the tested lipid compositions. Taken together, the experimental data supports that the effects of membrane surface charge on the rupture kinetics are related to variations in the extent of vesicle destabilization prior to vesicle rupture. Given the wide range of lipid compositions amenable to AH peptide-mediated vesicle rupture, this work further suggests that AH peptide is largely unique among membrane-active peptides, thereby substantiating its position as a promising broad-spectrum antiviral agent.

    View details for DOI 10.1021/jp411648s

    View details for Web of Science ID 000333948200015

    View details for PubMedID 24628664

  • Vesicle Adhesion and Rupture on Silicon Oxide: Influence of Freeze-Thaw Pretreatment LANGMUIR Jackman, J. A., Zhao, Z., Zhdanov, V. P., Frank, C. W., Cho, N. 2014; 30 (8): 2152-2160


    We have investigated the effect of freeze-thaw (FT) pretreatment on the adhesion and rupture of extruded vesicles over a wide range of vesicle sizes. To characterize the size distributions of vesicles obtained with and without FT pretreatment, dynamic light scattering (DLS) experiments were performed. The interaction between extruded vesicles and a silicon oxide substrate was investigated by quartz crystal microbalance with dissipation (QCM-D) monitoring, with a focus on comparative analysis of similar-sized vesicles with and without FT pretreatment. Under this condition, there was a smaller mass load at the critical coverage associated with untreated vesicles, as compared to vesicles which had been subjected to FT pretreatment. In addition, the rupture of treated vesicles generally resulted in formation of a complete planar bilayer, while the adlayer was more heterogeneous when employing untreated vesicles. Combined with kinetic analysis and extended-DLVO model calculations, the experimental evidence suggests that the differences arising from FT pretreatment are due to characteristics of the vesicle size distribution and also multilamellarity of an appreciable fraction of untreated vesicles. Taken together, our findings clarify the influence of FT pretreatment on model membrane fabrication on solid supports.

    View details for DOI 10.1021/la404582n

    View details for Web of Science ID 000332494000029

    View details for PubMedID 24512463

  • Rupture of Lipid Vesicles by a Broad-Spectrum Antiviral Peptide: Influence of Vesicle Size JOURNAL OF PHYSICAL CHEMISTRY B Jackman, J. A., Zan, G. H., Zhdanov, V. P., Cho, N. 2013; 117 (50): 16117-16128


    An amphipathic α-helical (AH) peptide was recently discovered that can rupture the lipid envelope of many viruses including HIV, hepatitis C, dengue, and herpes simplex. Despite its broad-spectrum activity, the AH peptide specifically targets small viruses only and does not affect large viruses. Indirect observations of virus size-specific targeting have been confirmed in a model system comprised of intact lipid vesicles on a gold substrate. Depending on vesicle size, AH peptide can promote vesicle rupture, but the mechanism by which vesicle size influences the rupture process remains to be elucidated. Herein, using the dynamic light scattering and quartz crystal microbalance with dissipation techniques, we have combined experiment and theory to understand the effects of vesicle size on the interaction between the AH peptide and vesicles. We identified that the AH peptide-binding interaction can induce a structural rearrangement of the vesicle's lipid bilayer, which occurs independently of vesicle size. Kinetic analysis also revealed that AH peptide-binding occurs cooperatively for small vesicles only. Binding cooperativity is consistent with pore formation leading to vesicle rupture. By contrast, for large vesicles, AH peptide-binding is noncooperative and does not cause vesicle rupture, suggesting that the binding interaction occurs via a different mechanism. Compared to previous estimates that AH peptide is most effective against viruses with a diameter of less than 70 nm, our evidence validates that AH peptide may target a wider size range of enveloped viruses up to 160 nm in diameter. Taken together, our findings provide a quantitative rationale to understand the targeting specificity of AH peptide as a broad-spectrum antiviral drug candidate.

    View details for DOI 10.1021/jp409716p

    View details for Web of Science ID 000328920600021

    View details for PubMedID 24274467

  • Influence of Osmotic Pressure on Adhesion of Lipid Vesicles to Solid Supports LANGMUIR Jackman, J. A., Choi, J., Zhdanov, V. P., Cho, N. 2013; 29 (36): 11375-11384


    The adhesion of lipid vesicles to solid supports represents an important step in the molecular self-assembly of model membrane platforms. A wide range of experimental parameters are involved in controlling this process, including substrate material and topology, lipid composition, vesicle size, solution pH, ionic strength, and osmotic pressure. At present, it is not well understood how the magnitude and direction of the osmotic pressure exerted on a vesicle influence the corresponding adsorption kinetics. In this work, using quartz crystal microbalance with dissipation (QCM-D) monitoring, we have experimentally studied the role of osmotic pressure in the adsorption of zwitterionic vesicles onto silicon oxide. The osmotic pressure was induced by changing the ionic strength of the solvent across an appreciably wider range (from 25 to 1000 mM NaCl outside of the vesicle, and 125 mM NaCl inside of the vesicle, unless otherwise noted) compared to that used in earlier works. Our key finding is demonstration that, by changing osmotic pressure, all three generic types of the kinetics of vesicle adsorption and rupture can be observed in one system, including (i) adsorption of intact vesicles, (ii) adsorption and rupture after reaching a critical vesicle coverage, and (iii) rupture just after adsorption. Furthermore, theoretical analysis of pressure-induced deformation of adsorbed vesicles and a DLVO-type analysis of the vesicle-substrate interaction qualitatively support our observations. Taken together, the findings in this work demonstrate that osmotic pressure can either promote or impede the rupture of adsorbed vesicles on silicon oxide, and offer experimental evidence to support adhesion energy-based models that describe the adsorption and spontaneous rupture of vesicles on solid supports.

    View details for DOI 10.1021/la4017992

    View details for Web of Science ID 000330079900022

    View details for PubMedID 23901837

  • Biotechnology Applications of Tethered Lipid Bilayer Membranes MATERIALS Jackman, J. A., Knoll, W., Cho, N. 2012; 5 (12): 2637-2657

    View details for DOI 10.3390/ma5122637

    View details for Web of Science ID 000312608500012

  • Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development BIOINTERPHASES Jackman, J. A., Cho, N. 2012; 7 (1-4)


    As one of the most important interfaces in cellular systems, biological membranes have essential functions in many activities such as cellular protection and signaling. Beyond their direct functions, they also serve as scaffolds to support the association of proteins involved in structural support, adhesion, and transport. Unfortunately, biological processes sometimes malfunction and require therapeutic intervention. For those processes which occur within or upon membranes, it is oftentimes difficult to study the mechanism in a biologically relevant, membranous environment. Therefore, the identification of direct therapeutic targets is challenging. In order to overcome this barrier, engineering strategies offer a new approach to interrogate biological activities at membrane interfaces by analyzing them through the principles of the interfacial sciences. Since membranes are complex biological interfaces, the development of simplified model systems which mimic important properties of membranes can enable fundamental characterization of interaction parameters for such processes. We have selected the hepatitis C virus (HCV) as a model viral pathogen to demonstrate how model membrane platforms can aid antiviral drug discovery and development. Responsible for generating the genomic diversity that makes treating HCV infection so difficult, viral replication represents an ideal step in the virus life cycle for therapeutic intervention. To target HCV genome replication, the interaction of viral proteins with model membrane platforms has served as a useful strategy for target identification and characterization. In this review article, we demonstrate how engineering approaches have led to the discovery of a new functional activity encoded within the HCV nonstructural 5A protein. Specifically, its N-terminal amphipathic, α-helix (AH) can rupture lipid vesicles in a size-dependent manner. While this activity has a number of exciting biotechnology and biomedical applications, arguably the most promising one is in antiviral medicine. Based on the similarities between lipid vesicles and the lipid envelopes of virus particles, experimental findings from model membrane platforms led to the prediction that a range of medically important viruses might be susceptible to rupturing treatment with synthetic AH peptide. This hypothesis was tested and validated by molecular virology studies. Broad-spectrum antiviral activity of the AH peptide has been identified against HCV, HIV, herpes simplex virus, and dengue virus, and many more deadly pathogens. As a result, the AH peptide is the first in class of broad-spectrum, lipid envelope-rupturing antiviral agents, and has entered the drug pipeline. In summary, engineering strategies break down complex biological systems into simplified biomimetic models that recapitulate the most important parameters. This approach is particularly advantageous for membrane-associated biological processes because model membrane platforms provide more direct characterization of target interactions than is possible with other methods. Consequently, model membrane platforms hold great promise for solving important biomedical problems and speeding up the translation of biological knowledge into clinical applications.

    View details for DOI 10.1007/s13758-011-0018-2

    View details for Web of Science ID 000307442400018

    View details for PubMedID 22589061

  • pH-Driven Assembly of Various Supported Lipid Platforms: A Comparative Study on Silicon Oxide and Titanium Oxide LANGMUIR Cho, N., Jackman, J. A., Liu, M., Frank, C. W. 2011; 27 (7): 3739-3748


    Supported lipid platforms are versatile cell membrane mimics whose structural properties can be tailored to suit the application of interest. By identifying parameters that control the self-assembly of these platforms, there is potential to develop advanced biomimetic systems that overcome the surface specificity of lipid vesicle interactions under physiological conditions. In this work, we investigated the adsorption kinetics of vesicles onto silicon and titanium oxides as a function of pH. On each substrate, a planar bilayer and a layer of intact vesicles could be self-assembled in a pH-dependent manner, demonstrating the role of surface charge density in the self-assembly process. Under acidic pH conditions where both zwitterionic lipid vesicles and the oxide films possess near-neutral electric surface charges, vesicle rupture could occur, demonstrating that the process is driven by nonelectrostatic interactions. However, we observed that the initial rupturing process is insufficient for propagating bilayer formation. The role of electrostatic interactions for propagating bilayer formation differs for the two substrates; electrostatic attraction between vesicles and the substrate is necessary for complete bilayer formation on titanium oxide but is not necessary on silicon oxide. Conversely, in the high pH regime, repulsive electrostatic interactions can result in the irreversible adsorption of intact vesicles on silicon oxide and even a reversibly adsorbed vesicle layer on titanium oxide. Together, the results show that pH is an effective tool to modulate vesicle-substrate interactions in order to create various self-assembled lipid platforms on hydrophilic substrates.

    View details for DOI 10.1021/la104348f

    View details for Web of Science ID 000288970900068

    View details for PubMedID 21366275

  • Vesicle and bilayer formation of diphytanoylphosphatidylcholine (DPhPC) and diphytanoylphosphatidylethanolamine (DPhPE) mixtures and their bilayers' electrical stability COLLOIDS AND SURFACES B-BIOINTERFACES Andersson, M., Jackman, J., Wilson, D., Jarvoll, P., Alfredsson, V., Okeyo, G., Duran, R. 2011; 82 (2): 550-561


    Lipid bilayers are of interest in applications where a cell membrane mimicking environment is desired. The performance of the lipid bilayer is largely dependent on the physical and chemical properties of the component lipids. Lipid bilayers consisting of phytanoyl lipids have proven to be appropriate choices since they exhibit high mechanical and chemical stability. In addition, such bilayers have high electrical resistances. Two different phytanoyl lipids, 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) and 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhPE), and various combinations of the two have been investigated with respect to their behavior in aqueous solutions, their interactions with solid surfaces, and their electrical stability. Dynamic light scattering, nuclear magnetic resonance diffusion, and cryogenic transmission electron microscopy measurements showed that pure DPhPC as well as mixtures of DPhPC and DPhPE consisting of greater than 50% (mol%) DPhPC formed unilamellar vesicles. If the total lipid concentration was greater than 0.15g/l, then the vesicles formed solid-supported bilayers on plasma-treated gold and silica surfaces by the process of spontaneous vesicle adsorption and rupture, as determined by quartz crystal microbalance with dissipation monitoring and atomic force microscopy. The solid-supported bilayers exhibited a high degree of viscoelasticity, probably an effect of relatively high amounts of imbibed water or incomplete vesicle fusion. Lipid compositions consisting of greater than 50% DPhPE formed small flower-like vesicular structures along with discrete liquid crystalline structures, as evidenced by cryogenic transmission electron microscopy. Furthermore, electrophysiology measurements were performed on bilayers using the tip-dip methodology and the bilayers' capacity to retain its electrical resistance towards an applied potential across the bilayer was evaluated as a function of lipid composition. It was shown that the lipid ratio significantly affected the bilayer's electrical stability, with pure DPhPE having the highest stability followed by 3DPhPC:7DPhPE and 7DPhPC:3DPhPE in decreasing order. The bilayer consisting of 5DPhPC:5DPhPE had the lowest stability towards the applied electrical potential.

    View details for DOI 10.1016/j.colsurfb.2010.10.017

    View details for Web of Science ID 000285858200043

    View details for PubMedID 21071188

  • Interfacial Binding Dynamics of Bee Venom Phospholipase A(2) Investigated by Dynamic Light Scattering and Quartz Crystal Microbalance LANGMUIR Jackman, J. A., Cho, N., Duran, R. S., Frank, C. W. 2010; 26 (6): 4103-4112


    Bee venom phospholipase A(2) (bvPLA(2)) is part of the secretory phospholipase A(2) (sPLA(2)) family whose members are active in biological processes such as signal transduction and lipid metabolism. While controlling sPLA(2) activity is of pharmaceutical interest, the relationship between their mechanistic actions and physiological functions is not well understood. Therefore, we investigated the interfacial binding process of bvPLA(2) to characterize its biophysical properties and gain insight into how membrane binding affects interfacial activation. Attention was focused on the role of membrane electrostatics in the binding process. Although dynamic light scattering experiments indicated that bvPLA(2) does not lyse lipid vesicles, a novel, nonhydrolytic activity was discovered. We employed a supported lipid bilayer platform on the quartz crystal microbalance with dissipation sensor to characterize this bilayer-disrupting behavior and determined that membrane electrostatics influence this activity. The data suggest that (1) adsorption of bvPLA(2) to model membranes is not primarily driven by electrostatic interactions; (2) lipid desorption can follow bvPLA(2) adsorption, resulting in nonhydrolytic bilayer-disruption; and (3) this desorption is driven by electrostatic interactions. Taken together, these findings provide evidence that interfacial binding of bvPLA(2) is a dynamic process, shedding light on how membrane electrostatics can modulate interfacial activation.

    View details for DOI 10.1021/la903117x

    View details for Web of Science ID 000275226700051

    View details for PubMedID 20020725