Membrane Remodeling by the Collective Action of Caveolin-1

Area of Science:

• Cell Biology
• Biophysics
• Structural Biology

Background:

• Caveolin-1 (CAV1) proteins are crucial for cellular processes, forming 50-100nm invaginations in the plasma membrane.
• Recent cryo-electron microscopy revealed CAV1 protomers form disk-like 8S complexes embedded in the cytoplasmic leaflet.
• The biophysical mechanisms by which CAV1 drives membrane remodeling remain poorly understood.

Purpose of the Study:

• To elucidate the biophysical mechanisms of membrane remodeling mediated by CAV1-8S complexes.
• To investigate how CAV1-8S complex interactions lead to membrane curvature and invagination.

Main Methods:

• Development of a novel bottom-up coarse-grained computational model to simulate large CAV1-8S systems.
• Molecular dynamics simulations to observe complex coordination and membrane interactions.

Main Results:

• Simulations revealed that CAV1-8S complexes coordinate through attractive electrostatic interactions between scaffolding domains.
• Complex coordination strongly correlates with membrane protrusion, as approaching complexes amplify stress in the exoplasmic leaflet.
• The proximity of CAV1-8S complexes induces dynamic curvature generation, potentially facilitating signaling partner access.

Conclusions:

• CAV1-8S complex coordination is a key mechanism for generating membrane curvature and facilitating cellular signaling.
• This study provides a computational framework to understand large-scale membrane remodeling driven by protein complexes.