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Cell Rep. 2017 Dec 5;21(10):2714-2723. doi: 10.1016/j.celrep.2017.11.040.

Mechanotransmission and Mechanosensing of Human alpha-Actinin 1.

Author information

1
Department of Physics, National University of Singapore, Singapore 117551, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
2
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
3
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
4
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.
5
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore. Electronic address: ms2001@columbia.edu.
6
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: phyyj@nus.edu.sg.

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.

KEYWORDS:

cytoskeleton; magnetic tweezers; mechanosensing; mechanostransmission; molecular shock absorber; single molecule manipulation; vinculin binding; α-actinin 1

PMID:
29212020
DOI:
10.1016/j.celrep.2017.11.040
[Indexed for MEDLINE]
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