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.
The ability to engineer a solvent-exposed surface of self-assembling coiled coils allows one to achieve a higher-order hierarchical assembly such as nano-or microfibers. Currently, these materials are being developed for a range of biomedical applications, including drug delivery systems; however, ways to mechanistically optimize the coiled-coil structure for drug binding are yet to be explored. Our laboratory has previously leveraged the functional properties of the naturally occurring cartilage oligomeric matrix protein coiled coil (C), not only for its favorable motif but also for the presence of a hydrophobic pore to allow for smallmolecule binding. This includes the development of Q, a rationally designed pentameric coiled coil derived from C. Here, we present a small library of protein microfibers derived from the parent sequences of C and Q bearing various electrostatic potentials with the aim to investigate the influence of higher-order assembly and encapsulation of candidate small molecule, curcumin. The supramolecular fiber size appears to be well-controlled by sequence-imbued electrostatic surface potential, and protein stability upon curcumin binding is well correlated to relative structure loss, which can be predicted by in silico docking.
Considerable effort has been devoted to generating novel protein-and peptide-based nanomaterials with their applications in a wide range of fields. Specifically, the unique property of proteins to self-assemble has been utilized to create a variety of nanoassemblies, which offer significant possibilities for next-generation biomaterials. In this minireview, we describe self-assembled protein-and peptide-based nanomaterials with focus on nanofibers and nanoparticles. Their applications in delivering therapeutic drugs and genes are discussed.
Previously reported, Q, is a thermoresponsive coiled-coil protein capable of higher-order supramolecular assembly into fibers and hydrogels with upper critical solution temperature (UCST) behavior. Here, we introduce a new coiled-coil...
Owing to their tunable properties, hydrogels comprised of stimuli sensitive polymers are one of the most appealing scaffolds with applications in tissue engineering, drug delivery and other biomedical fields. We...
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