(562g) Award Session: Impact of Collagen-like-Peptide (CLP) Triple Helix Design on CLP Melting Transition and Assembly: A Coarse-Grained Molecular Dynamics Simulation Study

Recent advances in materials design, synthesis, and simulation have allowed the creation of biomimetic materials with responsive yet controllable physicochemical properties. Materials that self-assemble into desired morphologies such as fibrils and supramolecular networks are of particular interest, where their ability to self-assemble can be tuned by applying external stimuli such as heat, light, pH, and salt for a range of applications including in drug delivery and tissue engineering. In this talk, I will present our recent coarse-grained (CG) molecular dynamics (MD) simulation studies on the melting transitions, fibrillar assembly, and gelation of collagen-like peptides (CLPs) as a guide for designing self-assembling peptide-based biomaterials. CLPs are thermoresponsive biopolymers in which each CLP chain is made up of repeat units of amino acid triplets, (X-Y-G), where X and Y are usually proline (P) and hydroxyproline (O), respectively. Like native collagen, CLPs have been shown to assemble to form triple helices, fibrils, and gels in aqueous solutions thus exhibiting self-assembly at multiple length scales. In this work, we extend our CG CLP model to simulate CLP heterotrimers in which the length of each of the three CLP strands forming the triple helix can be different. Inspired by the heterotrimeric nature of natural collagens, we investigate CLP heterotrimers with sticky ends which self-assemble to form fibrils and fibrillar networks driven by inter-chain and inter-helix hydrogen bonding. We explore how design parameters including the length and number of sticky ends in each CLP triple helix impact its thermal stability at low CLP triple helix concentration and assembly at varying CLP triple helix concentration. Overall, our work highlights the predictive capabilities of CG MD simulations in guiding experiments, as these complex peptide systems with unique molecular insights can inform new system designs and streamline the discovery of new, biomimetic platforms.