Molecular mechanisms of mechanotransduction in integrin-mediated cell-matrix adhesion

Abstract

Cell-matrix adhesion complexes are multi-protein structures linking the extracellular matrix (ECM) to the cytoskeleton. They are essential to both cell motility and function by bidirectionally sensing and transmitting mechanical and biochemical stimulations. Several types of cell-matrix adhesions have been identified and they share many key molecular components, such as integrins and actin-integrin linkers. Mechanochemical coupling between ECM molecules and the actin cytoskeleton has been observed from the single cell to the single molecule level and from immune cells to neuronal cells. However, the mechanisms underlying force regulation of integrin-mediated mechanotransduction still need to be elucidated. In this review article, we focus on integrinmediated adhesions and discuss force regulation of cell-matrix adhesions and key adaptor molecules, three different force-dependent behaviors, and molecular mechanisms for mechanochemical coupling in force regulation.

Receptor-mediated cell mechanosensing

“…, 2014 ). As physical linkages for the mechanochemical coupling between the ECM and the intracellular structures ( Li et al. , 2016b ), integrins have long been known for their role in mediating force transmission from the ECM across the cell membrane ( Volk et al.…”

Review of cellular mechanotransduction

“…Molecular mechanisms of force-induced integrin activation and cell-ECM adhesion are discussed in a couple of recent reviews [19, 20]. To learn about the evidence for a force-reinforced bond (a catch bond) in α5β1 integrins [21], one can read a recent review on the topic [22]. In contrast to integrins, only relative recently cell-cell adhesion molecule E-cadherin, critical for formation of an intact epithelial monolayer, is shown to be mechanosensors [23].…”

The Arf activator GBF1 localizes to plasma membrane sites involved in cell adhesion and motility

“…The bridging function is provided by integrins, heterodimeric transmembrane proteins that bind matrix components through their extracellular domains and interact with cytosolic focal adhesion proteins through their cytoplasmic tails (reviewed in. [18][19][20] ) One of the key components of focal adhesions is a-actinin, which binds both integrins and actin filaments to directly link the cytoplasmic tails of integrins to the actin cytoskeleton. 21 a-actinin is a homodimer that bundles actin filaments to increase the stiffness of stress fibers originating from focal adhesions.…”