All Subdomains of the Talin Rod Are Mechanically Vulnerable and May Contribute To Cellular Mechanosensing

Integrin-mediated adhesions have been a vital area of research in mechanotransduction. Integrins are known to provide a stable link between the extra cellular matrix and the cytoskeleton to facilitate mechanosensing, force generation and motility among many other processes. Integrins are also an integral part of focal adhesions, which are clusters of intracellular proteins that allow the bidirectional mechanical communication of cells with their surroundings..

Talin, is one of the main proteins in these integrin based focal adhesion complexes, and is essential for cellular spreading and to connect integrins with the actin cytoskeleton. Previous studies had showed that the N-terminal sub-region of the talin rod comprising the bundles R1-R3 increases the number of vinculin molecules (another key focal adhesion protein) bound to the talin molecule after force-induced stretching of this region. The fact that this region contains almost half of the vinculin binding sites of the entire talin rod led to the hypothesis that this region was the mechanosensitive part of the talin molecule, while the rest of the talin rod was responsible for force propagation.. However, the response of the remaining linear region to force has not been studied.

Recently, a collaborative effort from two research teams based at Imperial College London in the UK, and The University of Tampere in Finland have combined cutting edge single molecule atomic force microscopy (smAFM) and different cloning engineering strategies with steered molecular dynamics SMD simulations to demonstrate that indeed all domains of the talin rod can act as mechanosensors in cells, as all of them unfold over a physiological range of forces between 10 and 40 pN. The work published in the prestigious journal ACS Nano in an open access format that can be download from (http://pubs.acs.org/doi/abs/10.1021/acsnano.6b01658) opens new horizons for further studies that elucidate how the unfolding of the different regions of the talin rod molecule can affect precise sub-cellular and molecular mechanisms

Talin is a crucial molecule in cell mechanics and understanding how its unfolding may affect its interaction with other proteins and furthermore determine the cell fate by triggering alternative downstream singalling is of fundamental relevance to understand how mechanical forces combine with biochemical signaling to produce an overall cellular response. Without knowing the intricacies of the processes by which cells manage mechanical forces, our knowledge of cell behavior would be limited.

This research study showed clear understanding of principles and mechanisms of talin-mediated mechanotransduction which may provide crucial insights into the biological study health and diseases.