Caveolae mechanics in cellular functions and disease

Caveolae are small, cup-shaped invaginations of the plasma membrane that are enriched in caveolin and cavin proteins, cholesterol and glycosphingolipids. These specialized nanodomains serve diverse functions across numerous cell types; for example, they regulate nitric oxide signalling and transcytosis in endothelial cells, whereas in adipocytes and muscle cells they contribute to lipid homeostasis and mechanoprotection. In this Review, we highlight recent advances in caveolae biology, with a particular focus on structural insights from super-resolution microscopy and high-resolution cryo-electron microscopy of caveolin oligomers. We examine the molecular organization and resting-state dynamics of caveolar components, and explore how their metastable architecture enables rapid disassembly in response to mechanical and biochemical stimuli. We focus on caveolae-mediated mechanosensing, membrane protection and mechanotransduction, discussing how caveolae mechanics govern key cellular processes and interface with other mechanosensitive systems. Finally, we examine emerging evidence linking impaired caveolae mechanosensitivity to a variety of pathologies, and discuss how a deeper understanding of caveolae mechanics may inform the development of novel diagnostic and therapeutic strategies.