Mechanochemical coupling of formin-induced actin interaction at the level of single molecular complex
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ORIGINAL PAPER
Mechanochemical coupling of formin‑induced actin interaction at the level of single molecular complex Zhenhai Li1,2 · Hyunjung Lee1 · Suzanne G. Eskin1 · Shoichiro Ono3 · Cheng Zhu1,4 · Larry V. McIntire1 Received: 6 May 2019 / Accepted: 24 December 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Formins promote actin assembly and are involved in force-dependent cytoskeletal remodeling. However, how force alters the formin functions still needs to be investigated. Here, using atomic force microscopy and biomembrane force probe, we investigated how mechanical force affects formin-mediated actin interactions at the level of single molecular complexes. The biophysical parameters of G-actin/G-actin (GG) or G-actin/F-actin (GF) interactions were measured under force loading in the absence or presence of two C-terminal fragments of the mouse formin mDia1: mDia1Ct that contains formin homology 2 domain (FH2) and diaphanous autoregulatory domain (DAD) and mDia1Ct-ΔDAD that contains only FH2. Under force-free conditions, neither association nor dissociation kinetics of GG and GF interactions were significantly affected by mDia1Ct or mDia1Ct-ΔDAD. Under tensile forces (0–7 pN), the average lifetimes of these bonds were prolonged and molecular complexes were stiffened in the presence of mDia1Ct, indicating mDia1Ct association kinetically stabilizes and mechanically strengthens bonds of the dimer and at the end of the F-actin under force. Interestingly, mDia1Ct-ΔDAD prolonged the lifetime of GF but not GG bond under force, suggesting the DAD domain is critical for mDia1Ct to strengthen GG interaction. These data unravel the mechanochemical coupling in formin-induced actin assembly and provide evidence to understand the initiation of formin-mediated actin elongation and nucleation. Keywords Formin · Actin · Mechanotransduction · Atomic force microscopy (AFM) · Single-molecule biophysics
1 Introduction
Zhenhai Li and Hyunjung Lee: Co-first authors. Shoichiro Ono, Cheng Zhu and Larry V. McIntire: Co-correspoding authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10237-019-01284-5) contains supplementary material, which is available to authorized users. * Shoichiro Ono [email protected] * Cheng Zhu [email protected] * Larry V. McIntire [email protected] 1
Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive NW, Atlanta, GA 30332, USA
The actin cytoskeleton, a force-bearing and force-generating structure of the cell, undergoes dynamic force loading, such as shear, tensile or compressive forces, and rearrangement during many cellular functions (Parsons et al. 2010). For example, actin filaments experience tension in stress fibers, cortex, contractile ring and compression in filopodia and lamellipodia in a range of forces, from less than 1 pN up to 100 pN per filament, and formin, mDia1, is a key player to control those actin networks (Zimmermann and Kovar 2
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