Zyxin Is Involved in Fibroblast Rigidity Sensing and Durotaxis

Key proteins present in the FA in mouse fibroblasts include integrin, paxillin, focal adhesion kinase (FAK), talin, vinculin and zyxin (Kanchanawong et al., 2010). Some proteins in the FA including zyxin have been implicated to function as mechanotransducers, which transmit mechanical signals from the extracellular environment to the cytoskeleton of the cell (Wang et al., 1993). Zyxin was first discovered as a component of cell-substrate adhesions that also localized to the termini of actin stress fibres (Beckerle, 1986). It acts as a mechanotransducer to sense and relay mechanical signals to the cell (Hirata et al., 2008a). Zyxin also facilitates reinforcement of the actin cytoskeleton in response to mechanical forces (Yoshigi et al., 2005; Hirata et al., 2008b) and aids cell migration (Drees et al., 1999). It has also been reported that zyxin shuttles between the FAs and nucleus depending on mechanical stimuli in the extracellular environment of the cell (Beckerle, 1997; Nix and Beckerle, 1997; Yoshigi et al., 2005). Knocking down zyxin results in defects in actin cytoskeleton remodelling and reinforcement, reduces stress fibre and FA formation, as well as cancer cell migration and invasion (Harborth et al., 2001; Hoffman et al., 2006; Yamamura et al., 2013). While these studies clearly show that zyxin is involved in cell’s mechanotransduction pathway, the role of zyxin in substrate rigidity sensing still remains unknown. Since rigidity sensing is a key mechanism observed in various cell contexts including durotaxis, we aim to elucidate the role of zyxin, specifically in rigidity sensing which leads to directed cell migration through durotaxis.