A bio-inspired silkworm 3D cocoon-like hierarchical self-assembled structure from π-conjugated natural aromatic amino acids.

The formation of spontaneous 3D self-assembled hierarchical structures from 1D nanofibers is a significant breakthrough in materials science. Overcoming the major challenges associated with developing these 3D structures, such as uncontrolled self-assembly, complex procedures, and machinery, has been a formidable task. However, the current discovery reveals that simple π-system (fluorenyl)-functionalized natural aromatic amino acids, phenylalanine (Fmoc-F) and tyrosine (Fmoc-Y), can form bio-inspired 3D cocoon-like structures. These structures are composed of entangled 1D nanofibers created through supramolecular self-assembly using a straightforward one-step process of solvent casting. The self-assembly process relies on π-π stacking of the fluorenyl (π-system) moieties and intermolecular hydrogen bonding between urethane amide groups. The cocoon-like structures are versatile and independent of concentration, temperature, and humidity, making them suitable for various applications. This discovery has profound implications for materials science and the developed advanced biomaterials, such as Fmoc-F and Fmoc-Y, can serve as flexible foundational components for constructing 3D fiber-based structures.

Collagen Mimicry with a Short Collagen Model Peptide.

Mimicking triple helix and fibrillar network of collagen through collagen model peptide(CMP) with short GPO tripeptide repeats is a great challenge. Herein, a minimalistic CMP comprising only five GPO repeats [(GPO)5 ] is presented. This novel approach involves the fusion of ultrashort peptide with the synergetic power of π-system and ß-sheet formation to short CMP (GPO)5 . Accordingly, a hydrogel-forming, fluorenylmethoxycarbonyl (Fmoc)-functionalized ultrashort peptide (NFGAIL) is fused at the N-terminus and phenylalanine at the C-terminus of (GPO)5 (Fmoc-NFGAIL-(GPO)5 -F-COOH, FmP-5GPO). At room temperature, it forms a robust triple helix in aqueous buffer solution and has a relatively high melting point of 35 °C. The fluorenyl motif stabilizes the triple helix by aromatic π-π interactions as in its absence, triple helix is not formed. NFGAIL, which forms a ß-sheet, also aids in triple helix stabilization via intermolecular hydrogen bonding and hydrophobic interactions. FmP-5GPO forms highly entangled nanofibrils with a micrometer length, which have excellent cell viability. The achievement of stable triple helix and fibrils in such a short CMP(FmP-5GPO) sequence is a challenging feat, and its significance in CMP-based biomaterials is undeniable. The present strategy highlights the potential for developing new CMP sequences through intelligent tuning of fusion peptides and GPO repeats.

A Novel Surfactant with Short Hydrophobic Head and Long Hydrophilic Tail Generates Vesicles with Unique Structural Feature.

Surfactant molecules typically have a long hydrophobic tail and a short hydrophilic head group. It remains unexplored if surfactants can have a short hydrophobic head group and a long hydrophilic tail. Designing such surfactants is a challenge as a lengthy hydrophilic tail would completely solubilize the molecules. In this context, herein, the Fmoc-functionalized Gly-Pro-Hyp (GPO) tripeptide repeat-based molecule (Fm-GPO) with fluorenyl moiety as a short hydrophobic head and peptide as a long hydrophilic tail is demonstrated as a reverse surfactant at physiological pH, for the first time. π-π stacking of the fluorenyl moieties and intermolecular hydrogen bonding between the peptide chains with extended polyproline-II structure promoted the self-assembly into spherical vesicles with a unique feature of a large hydrophilic area in the interior and exterior of the bilayer. The current Fm-GPO system offers a new class of surfactants with unique features that can aid in the design of drug-loaded vehicles, which can be target-specific as the peptide chain can be manipulated with different functional ultra-short peptide sequences.

Recombinant and genetic code expanded collagen-like protein as a tailorable biomaterial.

Collagen occurs in nature with a dedicated triple helix structure and is the most preferred biomaterial in commercialized medical products. However, concerns on purity, disease transmission, and the reproducibility of animal derived collagen restrict its applications and warrants alternate recombinant sources. The expression of recombinant collagen in different prokaryotic and eukaryotic hosts has been reported with varying degrees of success, however, it is vital to elucidate the structural and biological characteristics of natural collagen. The recombinant production of biologically functional collagen is restricted by its high molecular weight and post-translational modification (PTM), especially the hydroxylation of proline to hydroxyproline. Hydroxyproline plays a key role in the structural stability and higher order self-assembly to form fibrillar matrices. Advancements in synthetic biology and recombinant technology are being explored for improving the yield and biomimicry of recombinant collagen. It emerges as reliable, sustainable source of collagen, promises tailorable properties and thereby custom-made protein biomaterials. Remarkably, the evolutionary existence of collagen-like proteins (CLPs) has been identified in single-cell organisms. Interestingly, CLPs exhibit remarkable ability to form stable triple helical structures similar to animal collagen and have gained increasing attention. Strategies to expand the genetic code of CLPs through the incorporation of unnatural amino acids promise the synthesis of highly tunable next-generation triple helical proteins required for the fabrication of smart biomaterials. The review outlines the importance of collagen, sources and diversification, and animal and recombinant collagen-based biomaterials and highlights the limitations of the existing collagen sources. The emphasis on genetic code expanded tailorable CLPs as the most sought alternate for the production of functional collagen and its advantages as translatable biomaterials has been highlighted.