Hopping around an entropic barrier created by force

► Application of mechanical force on a single molecule introduces an entropic barrier separating the collapsed from a force-driven extended conformation of the molecule. ► The force-induced entropic barrier exhibits long distance to the transition state, up to tens of nanometers. ► The entropic barrier vanishes at zero force, and influences dramatically the kinetics of the molecule's transition between states. ► Langevin dynamics across such force induced barriers readily demonstrates the hopping behavior observed for a variety of single molecules placed under force. ► Such hopping is frequently misinterpreted as a manifestation of two-state folding/unfolding reactions observed in bulk experiments.