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

Fingerprint

Hydrogel
Hydrogels
Proteins
Molecules
Curcumin
Temperature
Phase behavior
Nanofibers
Forging
Structural analysis
Microscopic examination
Polymers
Fibers
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Thermoresponsive Protein-Engineered Coiled-Coil Hydrogel for Sustained Small Molecule Release. / Hill, Lindsay K.; Meleties, Michael; Katyal, Priya; Xie, Xuan; Delgado-Fukushima, Erika; Jihad, Teeba; Liu, Che Fu; O'Neill, Sean; Tu, Raymond S.; Renfrew, P. Douglas; Bonneau, Richard; Wadghiri, Youssef Z.; Montclare, Jin.

In: Biomacromolecules, 01.01.2019.

Research output: Contribution to journalArticle

Hill, LK, Meleties, M, Katyal, P, Xie, X, Delgado-Fukushima, E, Jihad, T, Liu, CF, O'Neill, S, Tu, RS, Renfrew, PD, Bonneau, R, Wadghiri, YZ & Montclare, J 2019, 'Thermoresponsive Protein-Engineered Coiled-Coil Hydrogel for Sustained Small Molecule Release', Biomacromolecules. https://doi.org/10.1021/acs.biomac.9b00107
Hill, Lindsay K. ; Meleties, Michael ; Katyal, Priya ; Xie, Xuan ; Delgado-Fukushima, Erika ; Jihad, Teeba ; Liu, Che Fu ; O'Neill, Sean ; Tu, Raymond S. ; Renfrew, P. Douglas ; Bonneau, Richard ; Wadghiri, Youssef Z. ; Montclare, Jin. / Thermoresponsive Protein-Engineered Coiled-Coil Hydrogel for Sustained Small Molecule Release. In: Biomacromolecules. 2019.
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