Thermoresponsive Protein-Engineered Coiled-Coil Hydrogel for Sustained Small Molecule Release

Lindsay K. Hill, Michael Meleties, Priya Katyal, Xuan Xie, Erika Delgado-Fukushima, Teeba Jihad, Che Fu Liu, Sean O'Neill, Raymond S. Tu, P. Douglas Renfrew, Richard Bonneau, Youssef Z. Wadghiri, Jin Montclare

Research output: Contribution to journalArticle

Abstract

Thermoresponsive hydrogels are used for an array of biomedical applications. Lower critical solution temperature-type hydrogels have been observed in nature and extensively studied in comparison to upper critical solution temperature (UCST)-type hydrogels. Of the limited protein-based UCST-type hydrogels reported, none have been composed of a single coiled-coil domain. Here, we describe a biosynthesized homopentameric coiled-coil protein capable of demonstrating a UCST. Microscopy and structural analysis reveal that the hydrogel is stabilized by molecular entanglement of protein nanofibers, creating a porous matrix capable of binding the small hydrophobic molecule, curcumin. Curcumin binding increases the α-helical structure, fiber entanglement, mechanical integrity, and thermostability, resulting in sustained drug release at physiological temperature. This work provides the first example of a thermoresponsive hydrogel comprised of a single coiled-coil protein domain that can be used as a vehicle for sustained release and, by demonstrating UCST-type behavior, shows promise in forging a relationship between coiled-coil protein-phase behavior and that of synthetic polymer systems.

Original languageEnglish (US)
JournalBiomacromolecules
DOIs
StateAccepted/In press - Jan 1 2019

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ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Hill, L. K., Meleties, M., Katyal, P., Xie, X., Delgado-Fukushima, E., Jihad, T., Liu, C. F., O'Neill, S., Tu, R. S., Renfrew, P. D., Bonneau, R., Wadghiri, Y. Z., & Montclare, J. (Accepted/In press). Thermoresponsive Protein-Engineered Coiled-Coil Hydrogel for Sustained Small Molecule Release. Biomacromolecules. https://doi.org/10.1021/acs.biomac.9b00107