Session: 04-09-01: Design of Engineering Materials

Paper Number: 168170

Molecular Dynamics Study of Transition Temperature and Phase Behavior in Elastin-Like Polypeptides of Varying Chain Lengths 

Elastin-like polypeptides (ELPs) are a class of recombinant biopolymers inspired by the structural protein elastin, which provides resilience and elasticity to tissues such as skin, lungs, and blood vessels. These biopolymers are composed of repeating pentapeptide motifs (Val-Pro-Gly-X-Gly), where the guest residue (X) can be modified to tune their physicochemical properties. A key characteristic of ELPs is their thermoresponsive behavior, undergoing a reversible phase transition at the lower critical solution temperature (LCST), shifting from a soluble to an aggregated state when the transition temperature (TT) is exceeded. This property, combined with their biocompatibility, biodegradability, and tunability, makes ELPs highly attractive in bioengineering for applications such as drug delivery, tissue scaffolding, and injectable biomaterials. However, a detailed molecular-level understanding of how chain length variations influence TT and phase behavior remains incomplete. In this study, we employ molecular dynamics (MD) simulations using GROMACS to investigate the temperature-dependent structural transitions of ELPs with varying chain lengths, offering new insights into their phase behavior at an atomistic scale.

Using multiscale material modeling, we characterize conformational changes, aggregation kinetics, and solvent interactions that govern ELP phase transitions. Our analysis quantifies the impact of chain length on TT by evaluating key thermodynamic properties such as solvent-accessible surface area, radius of gyration, and intermolecular interactions. We observe distinct aggregation patterns across different chain lengths, revealing how hydrophobic interactions and entropic contributions drive phase separation. These molecular insights provide a quantitative framework for predicting TT and optimizing ELP design for targeted applications.

A precise understanding of phase transition behavior is essential for designing scaffolds capable of dynamically modulating mechanical integrity, porosity, and bioactivity in response to physiological stimuli. While this study does not focus on direct scaffold fabrication, our findings lay the groundwork for developing thermoresponsive biomaterials with finely tuned phase behavior. By elucidating how molecular weight or chain length variations influence thermal responsiveness, our work informs future experimental studies aimed at optimizing ELP properties for scaffold development in tissue engineering. Furthermore, our simulations provide a predictive tool for engineering ELP sequences with customized phase behavior, facilitating the development of scaffolds that promote cell adhesion, proliferation, and extracellular matrix (ECM) deposition—key factors for successful tissue regeneration.

The implications of this study extend beyond fundamental biopolymer research, as understanding the relationship between ELP chain length and TT can facilitate the rational design of next-generation biomaterials. Future studies may explore additional factors such as ionic strength, pH variations, and sequence modifications to further refine ELP-based material systems. By integrating computational and experimental approaches, researchers can harness the tunability of ELPs to develop bioactive scaffolds that support cell adhesion, proliferation, and differentiation under physiological conditions. By advancing the molecular-scale understanding of ELP phase behavior, this study provides valuable insights into their self-assembly mechanisms and thermodynamic properties, offering a foundation for future biomaterial innovations.

Presenting Author: Praneel Singla San Diego State University

Presenting Author Biography: Currently a graduate student in the integrated 4+1 B.S./M.S. program at San Diego State University, pursuing a Bachelor of Science in Mechanical Engineering and a Master of Science in Bioengineering. Under the mentorship of Dr. Sara Adibi, I conduct research on biomaterials, utilizing atomistic modeling to investigate their mechanical behavior, self-healing properties, and potential biomedical applications. My work aims to advance the development of sustainable and reprocessable biomaterials, contributing to innovative solutions in bioengineering and future engineering applications.

Authors:

Praneel Singla San Diego State University
Sara Adibi San Diego State University