Caveolae are flask-shaped invaginations of the cell membrane present in most mechanically active cells. These structures may behave like two-dimensional springs and represent mechanotransduction organelles. Although a lipid bilayer is nearly inextensible, the cell membrane is capable of large changes in area during cell stretch or membrane tether extension. Bending of caveolae may provide the required change in apparent surface area. This suggests that caveolae concentrate mechanical deformations, serving as mechanical amplifiers while simultaneously reducing tension in the rest of the plasma membrane. The morphology of caveolae is dependent on a coating of caveolin protein on the inner surface, and deformation of the caveolae changes the interaction between caveolin monomers. Caveolin is a scaffolding molecule and organize src, ERK, and NOS signaling cassettes, and may link activation of those cassettes to mechanotransduction. The caveolin-1 (cav1) dependent caveolae of endothelial cells have been linked to transduction of shear and swelling stresses via NOS and chloride channels, although the stretch response seems to be independent of cav1. The assembly of signaling cassettes may be necessary for proper transmission of biochemical signals, independent of any deformation. Mature skeletal muscle expresses primarily caveolin-3 (cav3), which associates with dystrophin at membrane overlaying the Z-disc. The cav3 dependent caveolae link src kinase with multiple effectors, including TRPC1 channels and confer redox sensitivity to the channel, independent of mechanical stimulation. To determine whether caveolin-dependent signaling results derive from mechanical properties of caveolae or from the scaffolding function of caveolins is quite difficult, because interventions that disrupt caveolin-mediated scaffolding also disrupt the morphology of caveolae. However, the structural arrangement of caveolae is highly suggestive of direct mechanical effects that may be revealed by careful mechanical testing. For example, skeletal myoblasts have a viscoelastic response response to cyclic stretch that is consistent with simultaneous caveolae-resident and -nonresident mechanical sensors. This suggests that controlling the dynamic conditions of mechanical stimulation may emphasize effects related to deformation of caveolae over effects related to caveolin scaffolding.