Unfolding protein with an atomic force microscope: Force-fluctuation induced non-exponential kinetics

TL;DR

This paper demonstrates that external force fluctuations in atomic force microscopy can mimic complex protein behaviors, emphasizing the need for careful control of experimental noise to accurately interpret protein unfolding kinetics.

Contribution

It reveals how external fluctuations can artificially produce non-exponential kinetics in protein unfolding experiments, impacting data interpretation.

Findings

External fluctuations can be mistaken for intrinsic protein complexity.

Artificial non-exponential distributions can arise from experimental noise.

Highlighting the importance of controlling external noise in mechanical protein studies.

Abstract

We show that in experimental atomic force microscopy studies of the lifetime distribution of mechanically stressed folded proteins the effects of externally applied fluctuations can not be distinguished from those of internally present fluctuations. In certain circumstances this leads to artificially non-exponential lifetime distributions which can be misinterpreted as a signature of protein complexity. This work highlights the importance of fully characterizing and controlling external sources of fluctuation in mechanical studies of proteins before drawing conclusions on the physics at play on the molecular level.