Paul Joshua Hurst

All Publications

• Hierarchical Assembly of Conductive Fibers from Coiled-Coil Peptide Building Blocks ACS NANO Grosvirt-Dramen, A., Urbach, Z. J., Hurst, P. J., Kwok, C. E., Patterson, J. P., Wang, F., Hochbaum, A. I. 2025

  Abstract

  Biology provides many sources of inspiration for synthetic and multifunctional nanomaterials. Naturally evolved proteins exhibit specialized, sequence-defined functions and self-assembly behavior. Recapitulating their molecularly defined self-assembly behavior, however, is challenging in de novo proteins. Peptides, on the other hand, represent a more well-defined and rationally designable space with the potential for sequence-programmable, stimuli-responsive design for structure and function, making them ideal building blocks of bioelectronic interfaces. In this work, we design peptides that exhibit stimuli-responsive self-assembly and the capacity to transport electrical current over micrometer-long distances. A lysine-lysine (KK) motif inserted at solvent-exposed positions of a coiled-coil-forming peptide sequence introduces pH-dependent control over a transition from unordered to α-helical peptide structure. The ordered state of the peptide serves as a building block for the assembly of coiled coils and higher-order assemblies. Cryo-EM structures of these structures reveal a hierarchical organization of α-helical peptides in a cross coiled coil (CCC) arrangement. Structural analysis also reveals a β-sheet fiber phase under certain conditions and placements of the KK motif, revealing a complex and sensitive self-assembly pathway. Both solid-state and solution-based electrochemical characterizations show that CCC fibers are electronically conductive. Single-fiber conductive AFM measurement indicates that the solid-state electrical conductivity is comparable with bacterial cytochrome filaments. Solution-deposited fiber films approximately doubled the electroactive surface area of the electrode, confirming their conductivity in aqueous environments. This work establishes a stimuli-responsive peptide sequence element for balancing the order-disorder transitions in peptides to control their self-assembly into highly organized electronically conductive nanofibers.

  View details for DOI 10.1021/acsnano.4c17248

  View details for Web of Science ID 001440377200001

  View details for PubMedID 40052932

• Coacervation drives morphological diversity of mRNA encapsulating nanoparticles. The Journal of chemical physics Pert, E. K., Hurst, P. J., Waymouth, R. M., Rotskoff, G. M. 2025; 162 (7)

  Abstract

  The spatial arrangement of components within an mRNA encapsulating nanoparticle has consequences for its thermal stability, which is a key parameter for therapeutic utility. The mesostructure of mRNA nanoparticles formed with cationic polymers has several distinct putative structures: here, we develop a field theoretic simulation model to compute the phase diagram for amphiphilic block copolymers that balance coacervation and hydrophobicity as driving forces for assembly. We predict several distinct morphologies for the mesostructure of these nanoparticles, depending on salt conditions and hydrophobicity. We compare our predictions with cryogenic-electron microscopy images of mRNA encapsulated by charge altering releasable transporters. In addition, we provide a graphics processing unit-accelerated, open-source codebase for general purpose field theoretic simulations, which we anticipate will be a useful tool for the community.

  View details for DOI 10.1063/5.0235799

  View details for PubMedID 39968821

• Hybrid Photoiniferter and Ring-Opening Polymerization Yields One-Pot Anisotropic Nanorods MACROMOLECULAR RAPID COMMUNICATIONS Hurst, P., Yoon, J., Singh, R., Abouchaleh, M., Stewart, K. A., Sumerlin, B. S., Patterson, J. P. 2024: e2400100

  Abstract

  Polymerization-induced self-assembly (PISA) has emerged as a scalable one-pot technique to prepare block copolymer (BCP) nanoparticles. Recently, a PISA process, that results in poly(l-lactide)-b-poly(ethylene glycol) BCP nanoparticles coined ring-opening polymerization (ROP)-induced crystallization-driven self-assembly (ROPI-CDSA), was developed. The resulting nanorods demonstrate a strong propensity for aggregation, resulting in the formation of 2D sheets and 3D networks. This article reports the synthesis of poly(N,N-dimethyl acrylamide)-b-poly(l)-lactide BCP nanoparticles by ROPI-CDSA, utilizing a two-step, one-pot approach. A dual-functionalized photoiniferter is first used for controlled radical polymerization of the acrylamido-based monomer, and the resulting polymer serves as a macroinitiator for organocatalyzed ROP to form the solvophobic polyester block. The resulting nanorods are highly stable and display anisotropy at higher molecular weights (>12k Da) and concentrations (>20% solids) than the previous report. This development expands the chemical scope of ROPI-CDSA BCPs and provides readily accessible nanorods made with biocompatible materials.

  View details for DOI 10.1002/marc.202400100

  View details for Web of Science ID 001200056800001

  View details for PubMedID 38520318

• Ring-Opening Polymerization of Cyclic Esters and Carbonates with (Thio)urea/Cyclopropenimine Organocatalytic Systems. ACS macro letters Morodo, R., Dumas, D. M., Zhang, J., Lui, K. H., Hurst, P. J., Bosio, R., Campos, L. M., Park, N. H., Waymouth, R. M., Hedrick, J. L. 2024: 181-188

  Abstract

  Organocatalyzed ring-opening polymerization is a powerful tool for the synthesis of a variety of functional, readily degradable polyesters and polycarbonates. We report the use of (thio)ureas in combination with cyclopropenimine bases as a unique catalyst for the polymerization of cyclic esters and carbonates with a large span of reactivities. Methodologies of exceptionally effective and selective cocatalyst combinations were devised to produce polyesters and polycarbonates with narrow dispersities (D = 1.01-1.10). Correlations of the pKa of the various ureas and cyclopropenimine bases revealed the critical importance of matching the pKa of the two cocatalysts to achieve the most efficient polymerization conditions. It was found that promoting strong H-bonding interactions with a noncompetitive organic solvent, such as CH2Cl2, enabled greatly increased polymerization rates. The stereoselective polymerization of rac-lactide afforded stereoblock poly(lactides) that crystallize as stereocomplexes, as confirmed by wide-angle X-ray scattering.

  View details for DOI 10.1021/acsmacrolett.3c00716

  View details for PubMedID 38252690

• CryoEM reveals the complex self-assembly of a chemically driven disulfide hydrogel CHEMICAL SCIENCE Hurst, P., Mulvey, J. T., Bone, R. A., Selmani, S., Hudson, R. F., Guan, Z., Green, J. R., Patterson, J. P. 2024; 15 (3): 1106-1116

  Abstract

  Inspired by the adaptability of biological materials, a variety of synthetic, chemically driven self-assembly processes have been developed that result in the transient formation of supramolecular structures. These structures form through two simultaneous reactions, forward and backward, which generate and consume a molecule that undergoes self-assembly. The dynamics of these assembly processes have been shown to differ from conventional thermodynamically stable molecular assemblies. However, the evolution of nanoscale morphologies in chemically driven self-assembly and how they compare to conventional assemblies has not been resolved. Here, we use a chemically driven redox system to separately carry out the forward and backward reactions. We analyze the forward and backward reactions both sequentially and synchronously with time-resolved cryogenic transmission electron microscopy (cryoEM). Quantitative image analysis shows that the synchronous process is more complex and heterogeneous than the sequential process. Our key finding is that a thermodynamically unstable stacked nanorod phase, briefly observed in the backward reaction, is sustained for ∼6 hours in the synchronous process. Kinetic Monte Carlo modeling show that the synchronous process is driven by multiple cycles of assembly and disassembly. The collective data suggest that chemically driven self-assembly can create sustained morphologies not seen in thermodynamically stable assemblies by kinetically stabilizing transient intermediates. This finding provides plausible design principles to develop and optimize supramolecular materials with novel properties.

  View details for DOI 10.1039/d3sc05790a

  View details for Web of Science ID 001126233000001

  View details for PubMedID 38239701

  View details for PubMedCentralID PMC10793653

• 3D Visualization of Proteins within Metal-Organic Frameworks via Ferritin-Enabled Electron Microscopy ADVANCED FUNCTIONAL MATERIALS Dhaoui, R., Cazarez, S., Xing, L., Baghdadi, E., Mulvey, J., Idris, N., Hurst, P., Vena, M., Palma, G., Patterson, J. 2024; 34 (13)

  View details for DOI 10.1002/adfm.202312972

  View details for Web of Science ID 001125100000001

• The role of protein folding in prenucleation clusters on the activity of enzyme@metal-organic frameworks JOURNAL OF MATERIALS CHEMISTRY A Carpenter, B. P., Rose, B., Olivas, E. M., Navarro, M. X., Talosig, A., Hurst, P. J., Di Palma, G., Xing, L., Guha, R., Copp, S. M., Patterson, J. P. 2024; 12 (2): 813-823

  View details for DOI 10.1039/d3ta05397k

  View details for Web of Science ID 001119723500001