Fatigue at the Molecular Scale

Abstract

The influence of force on the stability of inter- and intramolecular bonds has been studied in great detail. Experiments, e.g. with AFMs or the Biomembrane Force Probe, have shown that the relationship between the lifetime of biomolecules and applied forces is well described by the Bell equation. However, rather than experiencing a constant (or continuously increasing) force, some biomolecules are subject to repeated force cycles. For instance, myosin motors in muscles experience millions of force cycles over their lifetime. At the macroscopic level, repeated stress cycles can lead to ‘fatigue failure’. Fatigue failure originates in permanent micro-damages and occurs at subcritical stress levels, provided that the number of stress cycles is large enough. Fatigue is a major cause of failure in machinery; however there is no comprehensive theory of fatigue. To design machines, engineers use heuristic methods such as the Palmgren-Miner rule or S-N diagrams. Here, we investigate for the first time a molecular theory of fatigue failure. We aim to provide a theoretical basis for the heuristic methods engineers use to avoid fatigue failure and draw conclusions about the design of molecular machines such as kinesin or myosin motors.