Abstract

Cell membranes, complex assemblies of lipids and proteins, serve as dynamic platforms for numerous essential cellular processes. The precise functional state of membrane proteins and peptides is critically dependent on their immediate lipid environment. This study investigates the molecular mechanisms by which the lipid composition of the bilayer dictates the structural and functional adaptation of embedded proteins and transiently associated peptides. Using a combination of advanced computational modeling, including molecular dynamics simulations, and biophysical techniques, we explore the reciprocal interactions between various lipid species (e.g., cholesterol, phosphoinositides) and diverse membrane-associated molecules. Our key findings reveal that specific lipid-protein interactions induce subtle yet significant conformational changes in the protein structure, modulating activity, oligomerization, and lateral diffusion. Furthermore, we demonstrate how lipid-induced membrane curvature and mechanical tension can act as allosteric regulators. These results provide a deeper understanding of how cells utilize lipid heterogeneity to fine-tune membrane protein function, offering new insights into the pathogenesis of lipid-related disorders and guiding the rational design of membrane-targeting therapeutics.