BMB Reports 2018; 51(12): 623-629
Cellular machinery for sensing mechanical force
Chul-Gyun Lim#, Jiyoung Jang# and Chungho Kim*
Department of Life Sciences, Korea University, Seoul 02841, Korea
Correspondence to: *Corresponding author. Tel: +82-2-3290-3402; Fax: +82-2-3290-4144; E-mail:
#These authors contributed equally to this work.
Received: September 19, 2018; Published online: December 31, 2018.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
For mechanical force to induce changes in cellular behaviors, two main processes are inevitable; perception of the force and response to it. Perception of mechanical force by cells, or mechanosensing, requires mechanical force-induced conformational changes in mechanosensors. For this, at least one end of the mechanosensors should be anchored to relatively fixed structures, such as extracellular matrices or the cytoskeletons, while the other end should be pulled along the direction of the mechanical force. Alternatively, mechanosensors may be positioned in lipid bilayers, so that conformational changes in the embedded sensors can be induced by mechanical force-driven tension in the lipid bilayer. Responses to mechanical force by cells, or mechanotransduction, require translation of such mechanical force-induced conformational changes into biochemical signaling. For this, protein-protein interactions or enzymatic activities of mechanosensors should be modulated in response to force-induced structural changes. In the last decade, several molecules that met the required criteria of mechanosensors have been identified and proven to directly sense mechanical force. The present review introduces examples of such mechanosensors and summarizes their mechanisms of action.
Keywords: Lipid bilayer model, Mechanical force, Mechanosensors, Tethered model
Fig. 1. Hypothetical schematic model for mechanosensing mechanisms of various types of mechanosensors. (A) The cytoskeletal proteins linked to the actin cytoskeleton (F-actin) and adhesive structures that can undergo structural changes in response to mechanical force. The structural change can expose a binding site for other proteins to interact with, which can induce biochemical signaling. (B) Force acting on the ECM-tethered latency-associated peptide (LAP) by cells via integrin can induce a structural change in LAP. Due to the structural change, transforming growth factor (TGF) β can be released from the LAP complex. RGD; Arg-Gly-Asp (integrin binding site), ECM; extracellular matrix. (C) A stretchgated ion channel in Drosophila, NOMPC (no mechanoreceptor potential C), embedded in the membrane. Two of its four subunits are shown. S6 helices from each subunit block the passage of ions. These helices are linked to TRP domains that are captured by the cytoplasmic domains of the channel (left). The mechanical force that can stretch the cytoplasmic domain tethered to the microtubule can induce disposition of the TRP domains, which in turn induce structural changes in the S6 helices, leading to the opening of the channel (right). (D) The closed conformation of the TRAAK channel adopts a wedge shape, causing distortion of the lipid bilayer nearby (left). The open conformation of the channel adopts a cylinder shape (right). The projection areas of the cross-sections of the channel (yellow dotted lines) are shown in both the conformations. (E) Schematic illustrations of two subunits of Piezo1 are shown. Each of its three subunits has a curved conformation in the lipid bilayer, making a ‘dimple’ on the membrane (left). The central pore is suggested to be opened by tension in the lipid bilayer, which may flatten out the subunits (right).

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