Figure 4.

Schematic integrating the role of caveolae in mechanosensing (including ECM stiffness) and mechanotransduction (including cytoskeleton reshaping, and subsequent ECM remodelling). Caveolar structures exhibit high plasticity, such that upon reduced PM tension higher-order structures named ‘rosettes’ -vacuoles surrounded by clusters of caveolae connected through a single neck to the PM- are formed. Rosettes can flatten in response to mechanical challenges, such as shear stress, stretching or substrate stiffness, leading to the formation of single-pit caveolae. Further PM tension increase results in complete flattening and thus caveolae disassembly. Therefore, there is an inverse correlation between the complexity of Cav1-bound membrane and PM tension. Regulatory pathways integrate to control the plasticity, trafficking and mechanosensing and mechanostransducing abilities of caveolae, which lead to changes in the cytoskeleton, which in turn results in ECM remodeling through different effector mechanisms and in different functional outcomes for adapting to the surrounding mechanical stimuli. Created with BioRender.com accessed on 6 March 2023.