On the formation of caveolae and similar membrane invaginations

TL;DR

This paper presents a physical model explaining caveolae formation as membrane invaginations driven by asymmetric forces from proteins, without requiring cytoskeletal forces, matching several experimental observations.

Contribution

The study introduces a novel physical model for caveolae formation based on asymmetric protein forces, expanding understanding beyond cytoskeletal involvement.

Findings

Model explains caveolae sizes around 100nm

Predicts large variation in bud shapes

Accounts for size differences due to protein mutations

Abstract

We study a physical model for the formation of bud-like invaginations on fluid membranes under tension, and apply this model to caveolae formation. We demonstrate that budding can be driven by membrane-bound inclusions (proteins) provided that they exert asymmetric forces on the membrane that give rise to bending moments. In particular, Caveolae formation may not necessarily require forces to be applied by the cytoskeleton. Our theoretical model is able to explain several features observed experimentally in caveolae, where proteins in the caveolin family are known to play a crucial role in the formation of caveolae buds. These include (i) the formation of caveolae buds with sizes in the 100nm range (ii) that a fairly large variation of bud shape is expected (iii) that certain N and C termini deletion mutants result in vesicles that are an order of magnitude larger. Finally, we discuss the possible origin of the morphological striations that are observed on the surfaces of the caveolae.