Imaging Macromolecular Structural Dynamics with Low-Dose, Time-Resolved Transmission Electron Microscopy

Joseph Mckeown | 19-FS-038


The ability to measure macromolecular dynamics is key to gaining predictive mastery of biological systems. However, all well established experimental methods for investigating the structure of biological macromolecules have inherent spatial and/or temporal limitations to studying macromolecular dynamics.

Our research demonstrated that sufficient signal can be acquired from low-Z soft materials using dynamic transmission electron microscopy (DTEM) to, potentially, allow measurements of functionally relevant macromolecular motion. We established the feasibility of dynamic measurement of macromolecular motion or structural change under specific experimental conditions using low dose, time-resolved transmission electron microscopy. Damage mitigation using a pulsed electron source in the DTEM was a significant finding, providing a unique experimental platform. An enhanced study of structural dynamics could fundamentally change scientists' understanding of the way macromolecules work as molecular machines.

Impact on Mission

The results of our study enhanced Lawrence Livermore National Laboratory's expertise in the fields of electron microscopy and structural biology. This project advances the Laboratory's biosecurity mission area and its R&D challenge in chemical and biological countermeasures.