Soft Nanoparticle-Induced Permeability of Lipid Membranes: Interplay of Sequence and Hydrophobicity

Single-chain nanoparticles (SCNPs) represent a class of folded macromolecules that mimic biologically derived structures through the covalent cross-linking of polymer backbones. This study explores the interactions between SCNPs and lipid bilayers, focusing on the modulation of the membrane permeability and lipid dynamics. By employing coarse-grained Monte Carlo simulations, we investigate the behavior of diblock, triblock, and random copolymers of varying hydrophobicities and cross-linking densities in contact with lipid membranes. Our results reveal that the structural properties and sequence of SCNPs significantly influence their adsorption behavior and the resulting membrane permeability. Specifically, SCNPs can embed within bilayers, forming transient nanopores that facilitate solvent and ion transport, contingent upon the balance of hydrophobicity and cross-linking. We elucidate the mechanism by which SCNPs affect lipid flip-flop rates and bilayer stability, providing insights into their potential applications in targeted drug delivery and biomimetic material design.