Nanoscale Observation of Conformational Transformation of DNA Polymerase via Liquid-Cell Transmission Electron Microscopy.

In recent years, liquid-cell transmission electron microscopy (LC-TEM) has been developed as , dynamic characterization of nanoscale materials in the liquid, although the state-of-art focus is heavy materials such as metals, and alloys. Herein we present a practical and stable liquid cell fabricated with standard micro-electro-mechanical (MEM) processes on silicon wafers. The liquid cell is universal for commonly used TEM holder, which may not only keep the liquid available for several weeks, and it has been also proven protective factor from electron beam damage when characterizing biomolecules such as proteins and DNAs, which are typical light-element molecules. DNA polymerase has been successfully characterized in the physiological state (unlabeled in PBS buffer), providing single molecular resolution, the dynamic structural evolution of the molecules and the complex interactions. Although more understandings of this technique has to be explored in the future, as we have pointed out in the manuscript, this work has illustrated that the LC-TEM can also become a potential and promising strategy, besides to the cryo-TEM technique, in the high-resolution characterization of biomolecules, which may benefit relative researches and industry, such as molecular and structural biology, ecology, pharmacology and environmental sciences.