Membrane remodeling by the caveolin-1 8s oligomeric complex

Caveolin-1 is a scaffolding protein crucial for the formation of caveolae, specialized membrane structures that are involved in diverse cellular processes such as endocytosis, mechano-sensing, and lipid regulation. Recently, a unique structure of the 8S oligomeric complex of caveolin-1 was resolved by cryo-electron microscopy, providing a foundational basis for understanding its molecular mechanisms. In this study, we probe the membrane interactions of the oligomeric caveolin-1 complex in membrane lipid bilayers and vesicles. We performed coarse-grain molecular dynamics simulations to delineate the interactions of the palmitoylated and non-palmitoylated caveolin-1 with multi-component membranes. During the simulations, the caveolin-1 complex binds to the membranes, partially to one of the leaflets in a shallow monotopic arrangement. A remodeling of the lipids in its vicinity of the complex was observed in both vesicles and planar bilayers. However, the caveolin-1 complex binds to vesicles without inducing any significant change to the curvature, whereas it appears to induce increased curvature in the planar bilayers leading to the formation of highly curved nanodomains. Cholesterol and phosphoserine lipid enrichment, hallmarks of caveolin-1 binding, were observed in a membrane-topology dependent manner. The differential cholesterol clustering observed between vesicles and bilayers, highlights the curvature-dependent nature of caveolin-1-mediated lipid organization. Our work highlights the dual significance of lipid organization and membrane topology in the functional dynamics of caveolin-1, shedding light on its role in inducing and sensing membrane curvature, which is pivotal for various cellular processes.