  Sensors are the first element of the pathways that control the response of
cells to their environment. After chemical, the next most important cue is
mechanical, and protein complexes that produce or enable a chemical signal in
response to a mechanical stimulus are called mechanosensors. There is a sharp
distinction between sensing an external force or pressure/tension applied to
the cell, and sensing the mechanical stiffness of the environment. We call the
first mechanosensitivity of the 1st kind, and the latter mechanosensitivity of
the 2nd kind. There are two variants of protein complexes that act as
mechanosensors of the 2nd kind: producing either a one-off or a reversible
action. The latent complex of TGF-$\beta$ is an example of the one-off action:
on the release of active TGF-$\beta$ signal, the complex is discarded and needs
to be replaced. In contrast, focal adhesion kinase (FAK) in a complex with
integrin is a reversible mechanosensor, which initiates the chemical signal in
its active phosphorylated conformation, but can spontaneously return to its
closed folded conformation. Here we study the physical mechanism of the
reversible mechanosensor of the 2nd kind, using FAK as a practical example. We
find how the rates of conformation changes depend on the substrate stiffness
and the pulling force applied from the cell cytoskeleton. The results compare
well with the phenotype observations of cells on different substrates.
