ABSTRACT
The nanomechanical response of a folded single protein, the natural nanomachine responsible for myriad biological processes, provides insight into its function. The conformational flexibility of a folded state, characterized by its viscoelasticity, allows proteins to adopt different shapes to perform their function. Despite efforts, its direct measurement has not been possible so far. We present a direct and simultaneous measurement of the stiffness and internal friction of the folded domains of the protein titin using a special interferometer based atomic force microscope. We analyzed the data by carefully separating different contributions affecting the response of the experimental probe to obtain the folded state's viscoelasticity. Above â¼95 pN of force, the individual immunoglobulins of titin transition from an elastic solid-like native state to a soft viscoelastic intermediate.
