Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers

Hiroki Katsuta; Satoru Okuda; Kazuaki Nagayama; Hiroaki Machiyama; Satoru Kidoaki; Masashi Kato; Masahiro Sokabe; Takaki Miyata; Hiroaki Hirata

doi:10.1016/j.isci.2023.106090

Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers

iScience. 2023 Feb 1;26(3):106090. doi: 10.1016/j.isci.2023.106090. eCollection 2023 Mar 17.

Authors

Hiroki Katsuta^{1

2

3}, Satoru Okuda⁴, Kazuaki Nagayama⁵, Hiroaki Machiyama⁶, Satoru Kidoaki⁷, Masashi Kato³, Masahiro Sokabe^{1

8}, Takaki Miyata², Hiroaki Hirata^{1

9}

Affiliations

¹ Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
² Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
³ Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
⁴ WPI Nano Life Science Institute, Kanazawa University, Kanazawa 920-1192, Japan.
⁵ Department of Mechanical Systems Engineering, Graduate School of Science and Engineering, Ibaraki University, Hitachi 316-8511, Japan.
⁶ Department of Immunology, Tokyo Medical University, Tokyo 160-8402, Japan.
⁷ Division of Applied Molecular Chemistry, Institute for Materials Chemistry and Engineering, Kyushu University, Fukuoka 819-0395, Japan.
⁸ Human Information Systems Laboratories, Kanazawa Institute of Technology, Hakusan 924-0838, Japan.
⁹ Department of Applied Bioscience, Kanazawa Institute of Technology, Hakusan 924-0838, Japan.

Abstract

Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs relies on actin crosslinking by α-actinin. Upon reduction of α-actinin-mediated crosslinks, the myosin II activity induced flows of actin filaments and myosin II along SFs, leading to a decrease in traction force exertion to ECM. The fluidized SFs maintained their cable integrity probably through enhanced actin polymerization throughout SFs. A computational modeling analysis suggested that lowering the density of actin crosslinks caused viscous slippage of actin filaments in SFs and, thereby, dissipated myosin-generated force transmitting along SFs. As a cellular scale outcome, α-actinin depletion attenuated the ECM-rigidity-dependent difference in cell migration speed, which suggested that α-actinin-modulated SF mechanics is involved in the cellular response to ECM rigidity.

Keywords: Biological sciences; Biophysics; Cell biology.