Force is a signal that cells cannot ignore.
Bottom Line: Cells sense biochemical, electrical, and mechanical cues in their environment that affect their differentiation and behavior.The molecular details underlying how cells respond to force are only beginning to be understood.Here we review tools for probing force-sensitive proteins and highlight several examples in which forces are transmitted, routed, and sensed by proteins in cells.
Affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195-7290.Show MeSH
Related in: MedlinePlus
Mentions: Clusters of cell-adhesion proteins occur at focal adhesions and contain multiple mechanosensitive proteins involved in coupling transmembrane α/β-integrins to the actin network. The extracellular portion of α/β-integrins connects to fibronectin in the extracellular matrix (ECM) and exhibits classic catch-bond behavior, likely through an allosteric pathway (Kong et al., 2009). Contractile forces generated in the actomyosin network are transmitted through talin to the integrins and the ECM. Talin contains a C-terminal rod-like structure consisting of 13 α-helical bundles. Under ∼5 pN of tension, several α-helical bundles unfold, revealing binding sites for vinculin (Figure 2; del Rio et al., 2009; Yao et al., 2014). Vinculin binds to these cryptic sites with high affinity (nanomolar range), preventing the α-helical bundles from refolding and recruiting additional actin filaments (Ciobanasu et al., 2014; Yao et al., 2014). The onset of vinculin binding to talin correlates with an increase in the strength of the focal adhesion (Ciobanasu et al., 2014). An intracellular FRET sensor (Figure 1D) inserted into vinculin indicated that each vinculin in a stable focal adhesion supports an average of 2.5 pN, that recruitment of vinculin and force transmission are independently controlled processes, and that the ability of vinculin to transmit force determines whether a focal adhesion will assemble or disassemble under tension (Grashoff et al., 2010).
Affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195-7290.