Mechanotransmission and Mechanosensing of Human alpha-Actinin 1
Shimin Le,
Xian Hu,
Mingxi Yao,
Hu Chen,
Miao Yu,
Xiaochun Xu,
Naotaka Nakazawa,
Felix M. Margadant,
Michael P. Sheetz,
Jie Yan
Affiliations
Shimin Le
Department of Physics, National University of Singapore, Singapore 117551, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
Xian Hu
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Department of Biosciences, University of Oslo, 0316 Oslo, Norway
Mingxi Yao
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
Hu Chen
Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Lab for Soft Functional Materials Research, Department of Physics, Xiamen University, Xiamen, Fujian 361005, China
Miao Yu
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
Xiaochun Xu
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
Naotaka Nakazawa
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
Felix M. Margadant
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore
Michael P. Sheetz
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Corresponding author
Jie Yan
Department of Physics, National University of Singapore, Singapore 117551, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Centre for Bioimaging Sciences, National University of Singapore, Singapore 117546, Singapore; Corresponding author
Summary: α-Actinins, a family of critical cytoskeletal actin-binding proteins that usually exist as anti-parallel dimers, play crucial roles in organizing the framework of the cytoskeleton through crosslinking the actin filaments, as well as in focal adhesion maturation. However, the molecular mechanisms underlying its functions are unclear. Here, by mechanical manipulation of single human α-actinin 1 using magnetic tweezers, we determined the mechanical stability and kinetics of the functional domains in α-actinin 1. Moreover, we identified the force-dependence of vinculin binding to α-actinin 1, with the demonstration that force is required to expose the high-affinity binding site for vinculin binding. Further, a role of the α-actinin 1 as molecular shock absorber for the cytoskeleton network is revealed. Our results provide a comprehensive analysis of the force-dependent stability and interactions of α-actinin 1, which sheds important light on the molecular mechanisms underlying its mechanotransmission and mechanosensing functions. : α-Actinins are critical actin crosslinking proteins that organize actin cytoskeletal networks. Le et al. determine the mechanical stability and dynamics of human α-actinin 1 and the force-dependence of vinculin binding to α-actinin 1, which sheds light on the molecular mechanisms of mechanotransmission and mechanosensing. Keywords: α-actinin 1, cytoskeleton, mechanosensing, mechanostransmission, vinculin binding, magnetic tweezers, single molecule manipulation, molecular shock absorber
