Force-history dependence and cyclic mechanical reinforcement of actin filaments at the single molecular level

• Type of Material: Article
• Authors: Hyunjung Lee, Georgia Institute of Technology; Suzanne G. Eskin, Georgia Institute of Technology; Shoichiro Ono, Emory University; Cheng Zhu, Georgia Institute of Technology; Larry McIntire, Emory University
• Language: English
• Date: 2019-02-01
• Publisher: The Company of Biologists Ltd.
• Publication Version: Final Published Version
• Copyright Statement: © 2019. Published by The Company of Biologists Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1242/jcs.216911
• Title of Journal or Parent Work: Journal of Cell Science
• Volume: 132
• Issue: 4 (jcs216911)
• Start Page: 1
• End Page: 10
• Grant/Funding Information: This work was supported by the National Institutes of Health [grants R01 HL18671 to L.V.M., U01 CA214354 to C.Z. and R01 AR048615 to S.O.]. Deposited in PMC for release after 12 months.
• Keywords: Integrin; Muscle; Nucleotide; Forms catch bonds; ADP-ACTIN; Kinetics; Single-molecule biophysics; Science & Technology; Dynamics; Actin; Cell Biology; Thermal fluctuations; Atomic force microscopy (AFM); Life Sciences & Biomedicine; Mechanotransduction; Polymerization; Binding
• Research Categories: Biology, Cell; Biophysics, Medical; Biology, Molecular

Abstract

The actin cytoskeleton is subjected to dynamic mechanical forces over time and the history of force loading may serve as mechanical preconditioning. While the actin cytoskeleton is known to be mechanosensitive, the mechanisms underlying force regulation of actin dynamics still need to be elucidated. Here, we investigated actin depolymerization under a range of dynamic tensile forces using atomic force microscopy. Mechanical loading by cyclic tensile forces induced significantly enhanced bond lifetimes and different force-loading histories resulted in different dissociation kinetics in G-actin–G-actin and G-actin–F-actin interactions. Actin subunits at the two ends of filaments formed bonds with distinct kinetics under dynamic force, with cyclic mechanical reinforcement more effective at the pointed end compared to that at the barbed end. Our data demonstrate force-history dependent reinforcement in actin–actin bonds and polarity of the actin depolymerization kinetics under cyclic tensile forces. These properties of actin may be important clues to understanding regulatory mechanisms underlying actin-dependent mechanotransduction and mechanosensitive cytoskeletal dynamics.