title: Talin Dependent Mechanosensitivity of Cell Focal Adhesions.
abstract: A fundamental question in mechanobiology is how mechanical stimuli are sensed by mechanosensing proteins and converted into signals that direct cells to adapt to the external environment. A key function of cell adhesion to the extracellular matrix (ECM) is to transduce mechanical forces between cells and their extracellular environment. Talin, a cytoplasmic adapter essential for integrin-mediated adhesion to the ECM, links the actin cytoskeleton to integrin at the plasma membrane. Here, we review recent progress in the understanding of talin-dependent mechanosensing revealed by stretching single talin molecules. Rapid progress in single-molecule force manipulation technologies has made it possible to directly study the impact of mechanical force on talin's conformations and its interactions with other signaling proteins. We also provide our views on how findings from such studies may bring new insights into understanding the principles of mechanobiology on a broader scale, and how such fundamental knowledge may be harnessed for mechanopharmacology.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, 117411 Singapore ; Department of Physics, National University of Singapore, Singapore, 117542 Singapore ; Centre for Bioimaging Sciences, National University of Singapore, Singapore, 117546 Singapore.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, 117411 Singapore.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Yao
authors.affiliation: School of Biosciences, University of Kent, Canterbury, CT2 7NJ Kent UK.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Goult
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, 117411 Singapore ; Department of Biological Sciences, Columbia University, New York, NY 10027 USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
keywords: Cell adhesion; Magnetic tweezers; Mechanosensing; Talin; Vinculin