Molecular Electron Videography of Heterogeneous Polymer Networks and Protein Transformation

I will discuss my group’s recent efforts on “molecular electron videography” integrating liquid-phase transmission electron microscopy (TEM) imaging and molecular dynamics (MD) simulation. Together they can reveal molecular level structural features and dynamics of macromolecular systems in a native liquid environment via direct real-space and real-space imaging at nanometer resolution. I will cover two examples. The first is solvated polymer networked nanoparticles, whose spatial heterogeneity is mapped to reveal characteristic sizes of “blobs” of a few nanometers and tens of nanometer. We back map these blobs to MD simulated atomic coordinates to reveal the substructural motifs corresponding to the blobs and show these structural features affect the conformation change of the nanoparticles, which impact their applications in delivery and biomedicine. The second system is on membrane protein nanodiscs, where we are able to measure the nanodiscs mechanics from real-space fluctuations and showcase a few rare events of the protein breathing out of its most stable confirmation. We foresee the platform of molecular electron videography to provide molecular insights into solution-phase dynamics at the nanoscale.