Computational Characterization of Solute Permeability in Elastin-Like Polypeptide Membranes for Synthetic Cells

Abstract

Elastin-like polypeptides (ELPs) are versatile biopolymers for constructing synthetic cell membranes. Applications in biosynthesis, molecular secretion, and payload delivery require an understanding of the solute transport across ELP membranes. In this work, we integrate coarse-grained molecular dynamics simulations with the inhomogeneous solubility-diffusion (ISD) model to investigate the passive permeation of small solutes across ELP membranes of varying sequence composition and stability. We observe that mechanically robust ELP bilayers remain highly permeable to small solutes but exhibit an unexpected nonmonotonic dependence on solute hydrophobicity. By backmapping the coarse-grained bead solutes to all-atom resolution, we identify specific molecular motifs that may promote or suppress solute transport through the ELP membrane. Across different ELP systems, we find that water permeability is only weakly dependent upon membrane stability but strongly dependent upon the ELP hydrophilic guest residues. Compositional analyses suggest that the side-chain flexibility and hydrophilicity of the guest residues in the hydrophilic block modulate interfacial solvation and regulate water permeation. Our results provide a broad computational characterization of ELP membrane permeability and present a predictive tool to tune the sequence of ELP-based vesicles for the engineered passive transport of molecular cargoes.