Single-Molecule Force Spectroscopy: Experiments, Analysis, and Simulations

Fidan Sumbul (1) , Felix Rico (2)

1 LAI - Adhésion et Inflammation
2 Department of Physiology and Biophysics

The mechanical properties of cells and of subcellular components are important to obtain a mechanistic molecular understanding of biological processes. The quantification of mechanical resistance of cells and biomolecules using biophysical methods matured thanks to the development of nanotechnologies such as optical and magnetic tweezers, the biomembrane force probe and atomic force microscopy (AFM). The quantitative nature of force spectroscopy measurements has converted AFM into a valuable tool in biophysics. Force spectroscopy allows the determination of the forces required to unfold protein domains and to disrupt individual receptor/ligand bonds. Molecular simulation as a computational microscope allows investigation of similar biological processes with an atomistic detail. In this chapter, we first provide a step-by-step protocol of force spectroscopy including sample preparation, measurement and analysis of force spectroscopy using AFM and its interpretation in terms of available theories. Next, we present the background for molecular dynamics (MD) simulations focusing on steered molecular dynamics (SMD) and the importance of bridging of computational tools with experimental techniques

Keywords: Dynamic Force Spectroscopy; Atomic Force Microscopy; Steered Molecular Dynamics Simulations; Receptor-Ligand interactions

Domains: Physics [physics]; Physics [physics]; Biological Physics [physics.bio-ph]

Fidan Sumbul, Felix Rico. Single-Molecule Force Spectroscopy: Experiments, Analysis, and Simulations. Atomic Force Microscopy, Methods in Molecular Biology, pp.163-189, 2019. ⟨hal-02272098⟩