Molecular Mechanoneurobiology: An Emerging Angle to Explore Neural Synaptic Functions

Figure 2

Schematics of mechanical force activation of mechanosensitive proteins. (a) Cadherins. Cadherins consist of two distinct trans-binding conformations, a strand-swap dimer (forming slip bonds, i.e., force accelerates dissociation), and an X-dimer (forming catch bonds, i.e., force impedes dissociation). Upon mechanical force application, trans-interacting cadherins switch their X-dimeric conformations to the strand-swap dimer, converting catch bonds to slip bonds. (b) Integrins. Two signaling pathways exist for integrins. In the inside-out signaling pathway, intercellular proteins (e.g., talin and/or kindlin) transduce mechanical forces across the membrane, unbending integrins and exposing ligand-binding sites. In the outside-in signaling pathway, integrin’s ligand (e.g., fibronectin) binding to integrin’s headpiece induces local conformational changes. Mechanical force can further activate integrin’s to a long-lived state by downward moving α7 helix in either αA and/or βA domain, swinging out hybrid domain and separating α and β tails. Such activation can lead to recruiting the talin and/or kindlin to reorganize cytoskeleton. (c) Mechanosensitive ion channels. Mechanical force activates mechanosensitive ion channels through deforming cell membrane (i.e., the bilayer mechanism) and tethering the channels (e.g., the single-tether model and the dual-tether model). (d) Talin. Mechanical stretching of talins exposes latent binding sites for vinculins, converting the mechanical effect into biochemical signals.

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