Mechanosensitive ion channels (MSCs) have long been the only established 
molecular class of cell mechanosensors; however, in the last decade, a variety 
of non-channel type mechanosensor molecules have been identified. Many of them 
are focal adhesion-associated proteins that include integrin, talin, and actin. 
Mechanosensors must be non-soluble molecules firmly interacting with relatively 
rigid cellular structures such as membranes (in terms of lateral stiffness), 
cytoskeletons, and adhesion structures. The partner of MSCs is the membrane in 
which MSC proteins efficiently transduce changes in the membrane tension into 
conformational changes that lead to channel opening. By contrast, the integrin, 
talin, and actin filament form a linear complex of which both ends are typically 
anchored to the extracellular matrices via integrins. Upon cell deformation by 
forces, this structure turns out to be a portion that efficiently transduces the 
generated stress into conformational changes of composite molecules, leading to 
the activation of integrin (catch bond with extracellular matrices) and talin 
(unfolding to induce vinculin bindings). Importantly, this structure also serves 
as an "active" mechanosensor to detect substrate rigidity by pulling the 
substrate with contraction of actin stress fibers (SFs), which may induce talin 
unfolding and an activation of MSCs in the vicinity of integrins. A recent study 
demonstrates that the actin filament acts as a mechanosensor with unique 
characteristics; the filament behaves as a negative tension sensor in which 
increased torsional fluctuations by tension decrease accelerate ADF/cofilin 
binding, leading to filament disruption. Here, we review the latest progress in 
the study of those non-channel mechanosensors and discuss their activation 
mechanisms and physiological roles.