Seminars

Cells are subjected to various mechanical cues and challenges from their environment, which they must be able to both sense and respond to. The response may involve specific signalling pathways triggered by mechanical stress, but also survival-threatening challenges that must elicit fast response. Mechano-sensing may involves change of conformation of proteins under stress, such as the opening of mechanically-gated channels or the unfolding of adhesion proteins. Another class of mechano-sensing systems involves the assembly and disassembly of multi-protein complexes. In this talk, I will discuss the case of if membrane invaginations formed by the self-assembly of curvature-sensitive membrane proteins. I will first discuss the tension buffering effect through a thermodynamic model of invagination stability under tension based on the phase separation of membrane-associated proteins into invaginated, multi-component membrane domains. I will mostly focus on caveoale, small invaginated nanodomains at the plasma membrane of many cell types, and extend the model to tubular invagination such as those formed by BAR domain proteins. Next I will discuss mechanosensing by such complexes. After presenting experimental evidence - obtained by collaborators - of the role of caveolae mechanics in the control of different signaling pathway, I will in particular discuss the importance of the multi-component nature of caveolae, enriched in the curvature-generating membrane protein caveolin, and stabilised by the curvature-dependent binding of cytosolic proteins, including cavin which can form a rigid coat over the caveolin domains, and the ATPase EHD2 which can form ring-like oligomers at the caveolae neck.