(162x) Understanding the Impact of Sequence Length, Composition, and Dispersity on the Melting Transitions and Gelation of Collagen-like-Peptides (CLPs)

This poster focuses on our coarse-grained (CG) simulation studies on the self-assembly, gelation, and melting transitions of thermoresponsive peptides, specifically collagen-like peptides (CLPs). CLPs are biomimetic polymers that mimic the extracellular matrix protein, collagen, and are composed of repeat units of (X-Y-G), where X and Y are usually proline (P) and hydroxyproline (O) and G glycine. Three CLP strands associate to form the CLP triple helix, which is stabilized via inter-chain hydrogen bonding involving the amine (N-H) hydrogen of glycine and the carbonyl (C=O) oxygen of proline. At temperatures above the melting temperature, T_m, the CLP triple helix undergoes a melting transition and CLP strands dissociate as inter-chain hydrogen bonds are broken. Despite their utility, design of new sequences (e.g., non-native substitutions) to tailor the structure and properties of bulk materials over multiple length scales remains difficult, partly owing to challenges in the synthesis of these long sequences. To address this, innovative simulation-based approaches are needed for linking chemical structure to nano- and microstructure and gelation, establishing underlying design rules and providing predictive tools that add in new sequence designs. In this work, we first investigated CLP systems in which charged residues such as lysine (K) and aspartic acid (D) were incorporated to promote fibrillar assembly and gelation, thus mimicking the hierarchical nature of native collagen. Molecular dynamics (MD) simulations using our CG model have successfully demonstrated physical gelation for charged CLPs sequences. It also shows that physical gelation is not possible when CLP is comprised of only (POG) repeat units that lack net charge at neutral pH, in agreement with previous experimental studies. Furthermore, we then extended our model to simulate CLP heterotrimers in which each of the three CLP strands forming the triple helix has a different length and sequence. These CLP sequences more closely mimic natural collagen due to their heterotrimeric nature, and using our CG model, we observed that gelation occurs at high temperatures near the T_m of the CLP triple helix but saw no signs of gelation at lower temperatures when the CLP triple helix is fully intact. Overall, our work highlights the predictive capabilities of MD simulations in guiding experiments as these peptide systems are often costly and difficult to synthesize, thus streamlining the discovery of new, biomimetic platforms.