Mechanotransmission and Mechanosensing of Human alpha-Actinin 1.

Cell Rep

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. Electronic address:

Published: December 2017

AI Article Synopsis

  • α-Actinins are key cytoskeletal proteins that help organize actin filaments and are involved in focal adhesion development, but their functional mechanisms aren't fully understood.
  • Using magnetic tweezers, this study investigates the stability and behavior of human α-actinin 1 under mechanical stress, revealing how force affects its properties.
  • The research uncovers that α-actinin 1 acts like a molecular shock absorber in the cytoskeleton and highlights the critical role of force in enhancing vinculin binding to α-actinin 1.

Article Abstract

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.

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http://dx.doi.org/10.1016/j.celrep.2017.11.040DOI Listing

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