α-Helix Unwinding as Force Buffer in Spectrins

Hirohide Takahashi (1, 2) , Felix Rico (1) , Christophe Chipot (3, 4, 5) , Simon Scheuring (1, 2)

1 Bio-AFM-Lab - BIO-AFM-LAB Bio Atomic Force Microscopy Laboratory
2 Weill Medical College of Cornell University [New York]
3 Laboratoire International Associé Centre National de la Recherche Scientifique
4 Department of Physics [Illinois at Urbana-Champaign, USA]
5 LPCT - Laboratoire de Physique et Chimie Théoriques

Spectrins are cytoskeletal proteins located at the inner face of the plasma membrane, making connections between membrane anchors and the actin cortex, and between actin filaments. Spectrins share a common structure forming a bundle of 3 a-helices and play a major role during cell deformation. Here, we used high-speed force spectroscopy and steered molecular dynamics simulations to understand the mechanical stability of spectrin revealing a molecular force buffering function. We find that spectrin acts as a soft spring at short extensions (70-100Å). Under continuous external stretching, its α-helices unwind leading to a viscous mechanical response over larger extensions (100-300Å), represented by a constant-force plateau in force/extension curves. This viscous force buffering emerges from a quasi-equilibrium competition between disruption and reformation of a-helical hydrogen bonds. Our results suggest

Mots clés: AFM; Force Spectroscopy; High-Speed Force Spectroscopy; unfolding; unwinding

Domaines: Biophysique [physics.bio-ph]

Hirohide Takahashi, Felix Rico, Christophe Chipot, Simon Scheuring. α-Helix Unwinding as Force Buffer in Spectrins. ACS Nano, 2018, 12 (3), pp.2719-2727. ⟨10.1021/acsnano.7b08973⟩. ⟨hal-02106340⟩