Direct and simultaneous measurement of the stiffness and internal friction of a single folded protein

TL;DR

This study introduces a novel method to directly and simultaneously measure the stiffness and internal friction of a single folded protein, revealing its viscoelastic properties under force.

Contribution

It presents the first direct measurement technique for the viscoelasticity of a folded protein's domains using an interferometer-based atomic force microscope.

Findings

Titin's immunoglobulins transition from elastic to viscoelastic states above 95 pN.

The method separates different contributions affecting the protein's mechanical response.

Provides insights into the conformational flexibility of proteins under force.

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 analysed the data by carefully separating different contributions affecting the response of the experimental probe to obtain the folded state's viscoelasticity. Above ~ 95 pN of force, the individual immunoglobulins of titin transition from an elastic solid-like native state to a soft viscoelastic intermediate.