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

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posted on 2019-08-19, 14:42 authored by 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 Kim Montclare
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.

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