title: Kinetic Ductility and Force-Spike Resistance of Proteins from Single-Molecule Force Spectroscopy.
abstract: Ductile materials can absorb spikes in mechanical force, whereas brittle ones fail catastrophically. Here we develop a theory to quantify the kinetic ductility of single molecules from force spectroscopy experiments, relating force-spike resistance to the differential responses of the intact protein and the unfolding transition state to an applied mechanical force. We introduce a class of unistable one-dimensional potential surfaces that encompass previous models as special cases and continuously cover the entire range from ductile to brittle. Compact analytic expressions for force-dependent rates and rupture-force distributions allow us to analyze force-clamp and force-ramp pulling experiments. We find that the force-transmitting protein domains of filamin and titin are kinetically ductile when pulled from their two termini, making them resistant to force spikes. For the mechanostable muscle protein titin, a highly ductile model reconciles data over 10 orders of magnitude in force loading rate from experiment and simulation.
authors: Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors: Pilar
authors: P
authors: Cossio
authors: Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany. Electronic address: gerhard.hummer@biophys.mpg.de.
authors: Gerhard
authors: G
authors: Hummer
authors: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Attila
authors: A
authors: Szabo
mesh_terms: D001696:Biomechanical Phenomena; D064211:Connectin / Q000737:chemistry / Q000378:metabolism*; D064448:Filamins / Q000737:chemistry / Q000378:metabolism*; D018260:Gelsolin / Q000378:metabolism; D007700:Kinetics; D055595:Mechanical Phenomena; D000072417:Protein Domains; D013057:Spectrum Analysis
chemical_list: D064211:Connectin; D064448:Filamins; D018260:Gelsolin