Glassy Dynamics in an Intrinsically Disordered Protein

Abstract

Intrinsically disordered proteins (IDPs) are characterized by their extreme conformational flexibility which gives them unique functional advantages, such as acting as entropic springs in the cytoskeleton. Here, we investigate the dynamic mechanical properties of a model IDP derived from neurofilament tail domains. We use a single-molecule manipulation technique, magnetic tweezers, to force the protein out of equilibrium and observe the relaxation of its end-to-end extension. We observe that the protein's extension decreases logarithmically for hours. We explain our results in terms of a phenomenological model, originally developed for bulk glassy systems, that assumes the total extension change is the sum of many independent structural transitions. Such a model makes sense for bulk measurements but is surprising to observe in a single molecule. Yet, the model accounts for our observation of a nonmonotonic (Kovacs) relaxation when subjecting the protein to a multi-step force protocol. This 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 heterogenous population of folded states. To our knowledge, this is the first reported example of this type of glassiness in proteins.