Danielle Mai

All Publications

• Sequence-defined structural transitions by calcium-responsive proteins POLYMER CHEMISTRY Chang, M. P., Huang, W., Shambharkar, G. M., Hernandez, K. M., Mai, D. J. 2024

  View details for DOI 10.1039/d4py00907j

  View details for Web of Science ID 001357501000001

• Protease-Driven Phase Separation of Elastin-Like Polypeptides. Biomacromolecules Wirtz, B. M., Yun, A. G., Wick, C., Gao, X. J., Mai, D. J. 2024

  Abstract

  Elastin-like polypeptides (ELPs) are a promising material platform for engineering stimuli-responsive biomaterials, as ELPs undergo phase separation above a tunable transition temperature. ELPs with phase behavior that is isothermally regulated by biological stimuli remain attractive for applications in biological systems. Herein, we report protease-driven phase separation of ELPs. Protease-responsive "cleavable" ELPs comprise a hydrophobic ELP block connected to a hydrophilic ELP block by a protease cleavage site linker. The hydrophilic ELP block acts as a solubility tag for the hydrophobic ELP block, creating a temperature window in which the cleavable ELP reactant is soluble and the proteolytically generated hydrophobic ELP block is insoluble. Within this temperature window, isothermal, protease-driven phase separation occurs when a critical concentration of hydrophobic cleavage product accumulates. Furthermore, protease-driven phase separation is generalizable to four compatible protease-cleavable ELP pairings. This work presents exciting opportunities to regulate ELP phase behavior in biological systems using proteases.

  View details for DOI 10.1021/acs.biomac.4c00346

  View details for PubMedID 38980747

• Engineered selective biotoxin-binding hydrogels for toxin sequestration JOURNAL OF POLYMER SCIENCE Morris, M. A., Yang, Y., Mai, D. J., Olsen, B. D. 2024

  View details for DOI 10.1002/pol.20230788

  View details for Web of Science ID 001189218000001

• Single-molecule studies in polymer science JOURNAL OF POLYMER SCIENCE Qiang, Z., Ullal, C., Mai, D. 2024

  View details for DOI 10.1002/pol.20240150

  View details for Web of Science ID 001182450800001

• Spatially Controlled Uv Light Generation at Depth Using Upconversion Micelles. Advanced materials (Deerfield Beach, Fla.) Zhou, Q., Wirtz, B. M., Schloemer, T. H., Burroughs, M. C., Hu, M., Narayanan, P., Lyu, J., Gallegos, A. O., Layton, C., Mai, D. J., Congreve, D. N. 2023: e2301563

  Abstract

  Ultraviolet (UV) light can trigger a plethora of useful photochemical reactions for diverse applications, including photocatalysis, photopolymerization, and drug delivery. These applications typically require penetration of high energy photons deep into materials, yet delivering these photons beyond the surface is extremely challenging due to absorption and scattering effects. Triplet-triplet annihilation upconversion (TTA-UC) shows great promise to circumvent this issue by generating high energy photons from incident lower energy photons. However, molecules that facilitate TTA-UC usually have poor water solubility, limiting their deployment in aqueous environments. To address this challenge, a nanoencapsulation method is leveraged to fabricate water-compatible UC micelles, enabling on-demand UV photon generation deep into materials. Two iridium-based complexes are presented for use as TTA-UC sensitizers with increased solubilities that facilitate the formation of highly emissive UV-upconverting micelles. Furthermore, this encapsulation method is shown to be generalizable to nineteen UV-emitting UC systems, accessing a range of upconverted UV emission profiles with wavelengths as low as 350 nm. As a proof-of-principle demonstration of precision photochemistry at depth, UV-emitting UC micelles are used to photolyze a fluorophore at a focal point nearly a centimeter beyond the surface, revealing opportunities for spatially controlled manipulation deep into UV-responsive materials. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/adma.202301563

  View details for PubMedID 37548335

• Polymeric protagonists for biological processes. Nature chemistry Gudinas, A. P., Mai, D. J. 2023

  View details for DOI 10.1038/s41557-023-01219-9

  View details for PubMedID 37248342

• Gelation Dynamics during Photo-Cross-Linking of Polymer Nanocomposite Hydrogels. ACS polymers Au Burroughs, M. C., Schloemer, T. H., Congreve, D. N., Mai, D. J. 2023; 3 (2): 217-227

  Abstract

  Embedding nanomaterials into polymer hydrogels enables the design of functional materials with tailored chemical, mechanical, and optical properties. Nanocapsules that protect interior cargo and disperse readily through a polymeric matrix have drawn particular interest for their ability to integrate chemically incompatible systems and to further expand the parameter space for polymer nanocomposite hydrogels. The properties of polymer nanocomposite hydrogels depend on the material composition and processing route, which were explored systematically in this work. The gelation kinetics of network-forming polymer solutions with and without silica-coated nanocapsules bearing polyethylene glycol (PEG) surface ligands were investigated using in situ dynamic rheology measurements. Network-forming polymers comprised either 4-arm or 8-arm star PEG with terminal anthracene groups, which dimerize upon irradiation with ultraviolet (UV) light. The PEG-anthracene solutions exhibited rapid gel formation upon UV exposure (365 nm); gel formation was observed as a crossover from liquid-like to solid-like behavior during in situ small-amplitude oscillatory shear rheology. This crossover time was non-monotonic with polymer concentration. Far below the overlap concentration (c/c* ≪ 1), spatially separated PEG-anthracene molecules were subject to forming intramolecular loops over intermolecular cross-links, thereby slowing the gelation process. Near the polymer overlap concentration (c/c* ∼ 1), rapid gelation was attributed to the ideal proximity of anthracene end groups from neighboring polymer molecules. Above the overlap concentration (c/c* > 1), increased solution viscosities hindered molecular diffusion, thereby reducing the frequency of dimerization reactions. Adding nanocapsules to PEG-anthracene solutions resulted in faster gelation than nanocapsule-free PEG-anthracene solutions with equivalent effective polymer concentrations. The final elastic modulus of nanocomposite hydrogels increased with nanocapsule volume fraction, signifying synergistic mechanical reinforcement by nanocapsules despite not being cross-linked into the polymer network. Overall, these findings quantify the impact of nanocapsule addition on the gelation kinetics and mechanical properties of polymer nanocomposite hydrogels, which are promising materials for applications in optoelectronics, biotechnology, and additive manufacturing.

  View details for DOI 10.1021/acspolymersau.2c00051

  View details for PubMedID 37065714

  View details for PubMedCentralID PMC10103194

• Democratizing the rapid screening of protein expression for materials development MOLECULAR SYSTEMS DESIGN & ENGINEERING Morris, M. A., Bataglioli, R. A., Mai, D. J., Yang, Y., Paloni, J. M., Mills, C. E., Schmitz, Z. D., Ding, E. A., Huske, A. C., Olsen, B. D. 2022

  View details for DOI 10.1039/d2me00150k

  View details for Web of Science ID 000874769900001

• Turn on the Stereo: Engaging in Mentorship from all Directions CHEMICAL ENGINEERING PROGRESS Mai, D. J. 2022; 118 (3): 16

  View details for Web of Science ID 000771592300008

• Monomer-scale design of functional protein polymers using consensus repeat sequences JOURNAL OF POLYMER SCIENCE Chang, M. P., Huang, W., Mai, D. J. 2021

  View details for DOI 10.1002/pol.20210506

  View details for Web of Science ID 000701743700001

• Tuning Selective Transport of Biomolecules through Site-Mutated Nucleoporin-like Protein (NLP) Hydrogels. Biomacromolecules Yang, Y. J., Mai, D. J., Li, S., Morris, M. A., Olsen, B. D. 2021

  Abstract

  Natural selective filtering systems (e.g., the extracellular matrix, nuclear pores, and mucus) separate molecules selectively and efficiently, and the detailed understanding of transport mechanisms exploited in these systems provides important bioinspired design principles for selective filters. In particular, nucleoporins consist of consensus repeat sequences that are readily utilized for engineering repeat proteins. Here, the consensus repeat sequence of Nsp1, a yeast nucleoporin, is polymerized to form a nucleoporin-like protein (NLP) and mutated to understand the effect of sequence on selective transport. The hydrophilic spacers of the NLPs were redesigned considering net charge, charge distribution, and polarity. Mutations were made near to and far from the FSFG interacting domain to explore the role of highly conserved residues as a function of spatial proximity. A nuclear transport receptor-cargo complex, nuclear transport factor 2-green fluorescent protein (NTF2-GFP), was used as a model for changes in transport. For mutations of the charged spacer, some mutations of highly conserved charged residues were possible without knocking out selective transport of the NTF2, but the formation of regions of clustered negative charge has an unfavorable effect on nuclear transporter permeation. Thus, positive net charge and alternating positive and negative charge within the hydrophilic spacer are advantageous for recognition and selective transport. In the polarity panel, mutations that increased the interaction between NTF2-GFP and the gel led to decreased permeation of the NTF2-GFP due to blocking of the interface and inability of the NTF2-GFP to transport into the gel. Therefore, these results provide a strategy for tuning selective permeability of biomolecules using the artificially designed consensus repeat-based hydrogels.

  View details for DOI 10.1021/acs.biomac.0c01083

  View details for PubMedID 33428378

• 100th Anniversary of Macromolecular Science Viewpoint: Single-Molecule Studies of Synthetic Polymers ACS MACRO LETTERS Mai, D. J., Schroeder, C. M. 2020; 9 (9): 1332–41

  View details for DOI 10.1021/acsmacrolett.0c00523

  View details for Web of Science ID 000572840300019

• Glycoprotein Mimics with Tunable Functionalization through Global Amino Acid Substitution and Copper Click Chemistry. Bioconjugate chemistry Seifried, B. M., Qi, W., Yang, Y. J., Mai, D. J., Puryear, W. B., Runstadler, J. A., Chen, G., Olsen, B. D. 2020

  Abstract

  Glycoproteins and their mimics are challenging to produce because of their large number of polysaccharide side chains that form a densely grafted protein-polysaccharide brush architecture. Herein a new approach to protein bioconjugate synthesis is demonstrated that can approach the functionalization densities of natural glycoproteins through oligosaccharide grafting. Global amino acid substitution is used to replace the methionine residues in a methionine-enriched elastin-like polypeptide with homopropargylglycine (HPG); the substitution was found to replace 93% of the 41 methionines in the protein sequence as well as broaden and increase the thermoresponsive transition. A series of saccharides were conjugated to the recombinant protein backbones through copper(I)-catalyzed alkyne-azide cycloaddition to determine reactivity trends, with 83-100% glycosylation of HPGs. Only an acetyl-protected sialyllactose moiety showed a lower level of 42% HPG glycosylation that is attributed to steric hindrance. The recombinant glycoproteins reproduced the key biofunctional properties of their natural counterparts such as viral inhibition and lectin binding.

  View details for DOI 10.1021/acs.bioconjchem.9b00601

  View details for PubMedID 32078297

• Molecular anisotropy and rearrangement as mechanisms of toughness and extensibility in entangled physical gels PHYSICAL REVIEW MATERIALS Edwards, C. R., Mai, D. J., Tang, S., Olsen, B. D. 2020; 4 (1)

  View details for DOI 10.1103/PhysRevMaterials.4.015602

  View details for Web of Science ID 000509510600005

• Nucleopore-Inspired Polymer Hydrogels for Selective Biomolecular Transport. Biomacromolecules Yang, Y. J., Mai, D. J., Dursch, T. J., Olsen, B. D. 2018; 19 (10): 3905-3916

  Abstract

  Biological systems routinely regulate biomolecular transport with remarkable specificity, low energy input, and simple mechanisms. Here, the biophysical mechanisms of nuclear transport inspire the development of gels for recognition and selective permeation (GRASP). GRASP presents a new paradigm for specific transport and selective permeability, in which binding interactions between a biomolecule and a hydrogel lead to faster penetration of the gel. A molecular transport theory identifies key principles for selective transport: entropic repulsion of noninteracting molecules and affinity-mediated diffusion of multireceptor biomolecules through a walking mechanism. The ability of interacting molecules to walk through hydrogels enables enhanced permeability in polymer networks. To realize this theoretical prediction in a novel material, GRASP is engineered from a poly(ethylene glycol) network (entropic barrier) containing antibody-binding oligopeptides (affinity domains). GRASP is synthesized using simultaneous bioconjugation and polycondensation reactions. The elastic modulus, characteristic pore size, biomolecular diffusivity, and selective permeability are measured in the resulting materials, which are applied to regulate the transport of equally sized molecules by preferentially transporting a monoclonal antibody from a polyclonal mixture. Overall, this work presents rationally designed, nucleopore-inspired hydrogels that are capable of controlling biomolecular transport.

  View details for DOI 10.1021/acs.biomac.8b00556

  View details for PubMedID 30183264

• Stretching Dynamics of Single Comb Polymers in Extensional Flow MACROMOLECULES Mai, D. J., Saadat, A., Khomami, B., Schroeder, C. M. 2018; 51 (4): 1507–17

  View details for DOI 10.1021/acs.macromol.7b02759

  View details for Web of Science ID 000426618500028

• Single polymer dynamics of topologically complex DNA CURRENT OPINION IN COLLOID & INTERFACE SCIENCE Mai, D. J., Schroeder, C. M. 2016; 26: 28–40

  View details for DOI 10.1016/j.cocis.2016.08.003

  View details for Web of Science ID 000390744400005

• Topology-Controlled Relaxation Dynamics of Single Branched Polymers. ACS macro letters Mai, D. J., Marciel, A. B., Sing, C. E., Schroeder, C. M. 2015; 4 (4): 446-452

  Abstract

  In this work, we report the synthesis and direct observation of branched DNA polymers using single molecule techniques. Polymer topology plays a major role in determining the properties of advanced materials, yet understanding the dynamics of these complex macromolecules has been challenging. Here, we study the conformational relaxation dynamics of single surface-tethered comb polymers from high stretch in a microfluidic device. Our results show that the molecular topology of individual branched polymers plays a direct role on the relaxation dynamics of polymers with complex architectures. Macromolecular DNA combs are first synthesized using a hybrid enzymatic-synthetic approach, wherein chemically modified DNA branches and DNA backbones are generated in separate polymerase chain reactions, followed by a "graft-onto" reaction via strain-promoted [3 + 2] azide-alkyne cycloaddition. This method allows for the synthesis of branched polymers with nearly monodisperse backbone and branch molecular weights. Single molecule fluorescence microscopy is then used to directly visualize branched polymers, such that the backbone and side branches can be tracked independently using single- or dual-color fluorescence labeling. Using this approach, we characterize the molecular properties of branched polymers, including apparent contour length and branch grafting distributions. Finally, we study the relaxation dynamics of single comb polymers from high stretch following the cessation of fluid flow, and we find that polymer relaxation depends on branch grafting density and position of branch point along the main chain backbone. Overall, this work effectively extends single polymer dynamics to branched polymers, which allows for dynamic, molecular-scale observation of polymers with complex topologies.

  View details for DOI 10.1021/acsmacrolett.5b00140

  View details for PubMedID 35596311

• Template-Directed Synthesis of Structurally Defined Branched Polymers MACROMOLECULES Marciel, A. B., Mai, D. J., Schroeder, C. M. 2015; 48 (5): 1296–1303

  View details for DOI 10.1021/acs.macromol.5b00219

  View details for Web of Science ID 000350918700004

• Microfluidic systems for single DNA dynamics SOFT MATTER Mai, D. J., Brockman, C., Schroeder, C. M. 2012; 8 (41): 10560–72

  Abstract

  Recent advances in microfluidics have enabled the molecular-level study of polymer dynamics using single DNA chains. Single polymer studies based on fluorescence microscopy allow for the direct observation of non-equilibrium polymer conformations and dynamical phenomena such as diffusion, relaxation, and molecular stretching pathways in flow. Microfluidic devices have enabled the precise control of model flow fields to study the non-equilibrium dynamics of soft materials, with device geometries including curved channels, cross-slots, and microfabricated obstacles and structures. This review explores recent microfluidic systems that have advanced the study of single polymer dynamics, while identifying new directions in the field that will further elucidate the relationship between polymer microstructure and bulk rheological properties.

  View details for DOI 10.1039/c2sm26036k

  View details for Web of Science ID 000310829300005

  View details for PubMedID 23139700

  View details for PubMedCentralID PMC3489478

• Influence of Polyethyleneimine Graftings of Multi-Walled Carbon Nanotubes on their Accumulation and Elimination by and Toxicity to Daphnia magna ENVIRONMENTAL SCIENCE & TECHNOLOGY Petersen, E. J., Pinto, R. A., Mai, D. J., Landrum, P. F., Weber, W. J. 2011; 45 (3): 1133–38

  Abstract

  Modifications of carbon nanotubes (CNTs) for different applications may change their physicochemical properties such as surface charge. Assessments of the extent to which such modifications influence CNT ecotoxicity, accumulation, and elimination behaviors are needed to understand potential environmental risks these variously modified nanoparticles may pose. We have modified carbon-14 labeled multi-walled carbon nanotubes (MWNTs) with polyethyleneimine (PEI) surface coatings to increase their aqueous stability and to give them positive, negative, or neutral surface charges. Uptake and elimination behaviors of Daphnia magna exposed to PEI-coated and acid-modified MWNTs at concentrations of approximately 25 and 250 μg/L were quantified. PEI surface coatings did not appear to substantially impact nanotube accumulation or elimination rates. Although the PEI-modified nanotubes exhibited enhanced stability in aqueous solutions, they appeared to aggregate in the guts of D. magna in a manner similar to acid-treated nanotubes. The MWNTs were almost entirely eliminated by Daphnia fed algae during a 48 h elimination experiment, whereas elimination without feeding was typically minimal. Finally, PEI coatings increased MWNT toxicities, though this trend corresponded to the size of the PEI coatings, not their surface charges.

  View details for DOI 10.1021/es1030239

  View details for Web of Science ID 000286577100045

  View details for PubMedID 21182278

• Response of Sinorhizobium meliloti to elevated concentrations of cadmium and zinc APPLIED AND ENVIRONMENTAL MICROBIOLOGY Rossbach, S., Mai, D. J., Carter, E. L., Sauviac, L., Capela, D., Bruand, C., de Bruijn, F. J. 2008; 74 (13): 4218–21

  Abstract

  Whole-genome transcriptional profiling was used to identify genes in Sinorhizobium meliloti 1021 that are differentially expressed during exposure to elevated concentrations of cadmium and zinc. Mutant strains with insertions in metal-regulated genes and in genes encoding putative metal efflux pumps were analyzed for their metal sensitivities, revealing a crucial role for the SMc04128-encoded P-type ATPase in the defense of S. meliloti against cadmium and zinc stress.

  View details for DOI 10.1128/AEM.02244-07

  View details for Web of Science ID 000257446900032

  View details for PubMedID 18469129

  View details for PubMedCentralID PMC2446505