The ergodicity question when imaging DNA conformation using liquid cell electron microscopy

Abstract

Assessing the ergodicity of graphene liquid cell electron microscope measurements, we report that loop states of circular DNA interconvert reversibly and that loop numbers follow the Boltzmann distribution expected for this molecule in bulk solution, provided that the electron dose is low (80-keV electron energy and electron dose rate 1–20 e− Å−2 s−1). This imaging technique appears to act as a “slow motion” camera that reveals equilibrated distributions by imaging the time average of a few molecules without the need to image a spatial ensemble.