Priya Katyal

A pH-sensitive coiled-coil hydrogel is presented. A pH of 6 results in nanoparticles that are unable to undergo gelation, while pH levels closer to the isoelectric point allow for the formation of fibers that physically crosslink and form hydrogels.

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.

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.

Proteins are versatile macromolecules that can perform a variety of functions. In the past three decades, they have been commonly used as building blocks to generate a range of biomaterials. Owing to their flexibility, proteins can either be used alone or in combination with other functional molecules. Advances in synthetic and chemical biology have enabled new protein fusions as well as the integration of new functional groups leading to biomaterials with emergent properties. This review discusses protein‐engineered materials from the perspectives of domain‐based designs as well as physical and chemical approaches for crosslinked materials, with special emphasis on the creation of hydrogels. Engineered proteins that organize or template metal ions, bear noncanonical amino acids (NCAAs), and their potential applications, are also reviewed.

Engineered proteins provide an interesting template for designing fluorine-19 (¹⁹F) magnetic resonance imaging (MRI) contrast agents, yet progress has been hindered by the unpredictable relaxation properties of fluorine. Herein, we present the biosynthesis of a protein block copolymer, termed “fluorinated thermoresponsive assembled protein” (F-TRAP), which assembles into a monodisperse nanoscale micelle with interesting ¹⁹F NMR properties and the ability to encapsulate and release small therapeutic molecules, imparting potential as a diagnostic and therapeutic (theranostic) agent. The assembly of the F-TRAP micelle, composed of a coiled-coil pentamer corona and a hydrophobic, thermoresponsive elastin-like polypeptide core, results in a drastic depression in spin–spin relaxation (T₂) times and unaffected spin–lattice relaxation (T₁) times. The nearly unchanging T₁ relaxation rates and linearly dependent T₂ relaxation rates have allowed for detection via zero echo time ¹⁹F MRI, and the in vivo MR potential has been preliminarily explored using ¹⁹F magnetic resonance spectroscopy (MRS). This fluorinated micelle has also demonstrated the ability to encapsulate the small-molecule chemotherapeutic doxorubicin and release its cargo in a thermoresponsive manner owing to its inherent stimuli-responsive properties, presenting an interesting avenue for the development of thermoresponsive ¹⁹F MRI/MRS-traceable theranostic agents.

Using calmodulin as a model system, we present the possible effect of topological constraint on protein backbone dynamics and binding thermodynamics.

Tremendous effort has been dedicated to the design and assembly of bioinspired protein-based architectures with potential applications in drug delivery, tissue engineering, biosensing, and bioimaging. Here, we describe our strategy to generate fibers and bionanocomposites using the coiled-coil domain of cartilage oligomeric matrix protein (COMPcc). Our construct, Q, engineered by swapping particular regions of COMPcc to optimize surface charge, self-assembles to form nanofibers. The Q protein nanofibers can efficiently bind curcumin to form robust mesofibers that can be potentially used for drug delivery and biomedical applications. In addition, using the same Q protein, we describe the biotemplation of gold nanoparticles (AuNP) in the presence and absence of the hexahistidine tag (His-tag). The Q bearing His-tag·AuNP (Q·AuNP) readily deposits on electrode surfaces, while Q without His-tag·AuNP (Qx·AuNP) stabilizes the soluble protein·gold bionanocomposites for several days without aggregating.