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Mechanotransmission and Mechanosensing of Human Alpha-actinin 1

50 Pages Posted: 5 Apr 2018 Publication Status: Published

See all articles by Shimin Le

Shimin Le

National University of Singapore (NUS) - Department of Physics (NUS)

Xian Hu

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

Mingxi Yao

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

Hu Chen

Xiamen University - Department of Physics

Xiaochun Xu

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

Naotaka Nakazawa

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

Felix M. Margadant

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

Michael P. Sheetz

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

Jie Yan

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

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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. In this work, 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 as well as the mechanical strength of the α-actinin 1 dimerization interaction. 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. Based on the mechanical stability and kinetics of α-actinin 1, a novel role of the α-actinin 1 as molecular suspensions for the cytoskeleton network is revealed. Our results provide the first comprehensive analysis of the force dependent stability and interactions of α-actinin 1, which sheds new light on the molecular mechanisms underlying its mechanotransmission and mechanosensing functions.

Suggested Citation

Le, Shimin and Hu, Xian and Yao, Mingxi and Chen, Hu and Xu, Xiaochun and Nakazawa, Naotaka and Margadant, Felix M. and Sheetz, Michael P. and Yan, Jie, Mechanotransmission and Mechanosensing of Human Alpha-actinin 1 (2018). Available at SSRN: https://ssrn.com/abstract=3155921 or http://dx.doi.org/10.2139/ssrn.3155921
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Shimin Le

National University of Singapore (NUS) - Department of Physics (NUS)

2 Science Drive 3
Blk S12, Level 2
117551
Singapore

Xian Hu

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

Mingxi Yao

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

Hu Chen

Xiamen University - Department of Physics

Siming South Road 422-19
Xiamen, Siming 361005
China

Xiaochun Xu

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

Naotaka Nakazawa

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

Felix M. Margadant

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

Michael P. Sheetz (Contact Author)

National University of Singapore (NUS) - Mechanobiology Institute (MBI) ( email )

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

Jie Yan

National University of Singapore (NUS) - Mechanobiology Institute (MBI) ( email )

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

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