Talin, a molecular shock absorber

26 Sep 2016. NUS researchers have discovered that a protein, present in cells – talin – is able to sense and buffer cells against external forces.

A collaborative team comprising researchers from NUS, University of Kent and University of Cambridge in the UK, showed how a protein known as talin is able to sense mechanical forces exerted on a cell and buffer this force through stochastic unfolding and refolding of its multiple folded domains during mechanical stretching and relaxation. This study is led by Prof Jie YAN from the Department of Physics and the Mechanobiology Institute, NUS and Prof Michael SHEETZ from the Mechanobiology Institute, NUS [1].

Increased tension during mechanical stretching of talin drives unfolding of more domains, which in turn relaxes its tension. In contrast, during mechanical relaxation, the reduced tension drives refolding of domains, which causes tension to increase. As a result, the level of tension in talin fluctuates within a narrow range of 7-10 pN during talin stretching and relaxation over a large scale.

The physical principle revealed for talin as a force buffer is universal to any large protein that is comprised of a linear array of domains. Such proteins are often found as mechanical linkages at adhesion sites of a cell to its extracellular environment and to its neighboring cells. The mechanism revealed in this study suggests that all these proteins have the capability of buffering force in live cells within a certain range, protecting the cells from disruptive high tension that may damage the tissue. In addition, a tightly controlled tension range by such force-buffering proteins allows robust mechanosensitive interactions to take place. Through this mechanism, cells can remain mechanically stable and active.

Figure shows the partial structure of talin with the 13 rod domains (R1–R13) under tension conditions.

Reference

[1] Yao, M., Goult, B. T., Klapholz, B., Hu, X., Toseland, C.P., Guo, Y., Cong, P., Sheetz, M. P., and Yan, J. (2016). “The mechanical response of talin.” Nature Communications, 7: 11966.