Visualizing macromolecular complexes with in situ liquid scanning transmission electron microscopy

A central focus of biological research is understanding the structure/function relationship of macromolecular protein complexes. Yet conventional transmission electron microscopy techniques are limited to static observations. Here we present the first direct images of purified macromolecular protein complexes using in situ liquid scanning transmission electron microscopy. Our results establish the capability of this technique for visualizing the interface between biology and nanotechnology with high fidelity while also probing the interactions of biomolecules within solution. This method represents an important advancement towards allowing future high-resolution observations of biological processes and conformational dynamics in real-time.

► Electron microscopic imaging of biomolecules in fluid without freezing or fixation.
► Necessary first step towards visualizing protein dynamics with TEM.
► Nanolipoprotein discs naturally stack in solution due to electrostatic interactions.