Glassy behavior and memory effects in the elastic response of a disordered protein

We investigate the dynamic mechanical properties of an intrinsically-disordered protein derived from neurofilament tail domains. We use a single-molecule stretching technique, magnetic tweezers, to force a disordered polyprotein out of equilibrium, and observe the relaxation of its end-to-end extension. The relaxation is logarithmic and slow, enduring for minutes to hours. We explain our results in terms of a phenomenological model, originally developed for bulk glassy systems, that assumes relaxation is caused by the sum of many independent structural transitions with widely varying rates. Such a model makes sense for macroscopic systems but is surprising to observe in a single molecule. Yet, the model quantitatively accounts for both the force-dependence of the logarithmic relaxation, and our observation of a non-monotonic (Kovacs) relaxation when subjecting the protein to a multi-step force protocol. The Kovacs memory effect is an unambiguous signature that many independent and parallel structural transitions are contributing to the overall dynamic mechanical properties of the IDP. This is fundamentally different from previous examples of glassy behavior in folded proteins which rely on a heterogeneous population of conformations.