Structures Frozen in Time: Application of Basic Cryogenic Electron Microscopy in an Undergraduate Lab

Cryogenic electron microscopy (cryo-EM) is a powerful technique capable of characterizing large protein complexes that are otherwise impossible to characterize using traditional crystallography methods. Cryo-EM has played a pivotal role in our understanding of the structure-function relationship of the spike proteins on the COVID-19 viral capsule, allowing for the rapid development of therapeutics and vaccines in our quest to end the COVID-19 pandemic. The relevance of cryo-EM to this global event advocates for its incorporation into undergraduate chemistry curricula. In fact, highlighting the importance and applicability of a technique to students allows for a better retention of knowledge. Therefore, in this laboratory exercise, we introduce the concepts and application of cryo-EM as a structural characterization tool in an upper-year undergraduate class. Furthermore, with the aid of three-dimensional (3D) printing, the concepts of tomography are introduced, allowing students to understand the construction of a 3D model from a collection of 2D images through cryo-EM. According to student responses, this lab module was well-received, and the 3D-printed model indeed added to their learning experience. While cryo-EM is a specialized technique that may not be available to some educational institutions, those with access should consider its incorporation into their curriculum, thereby exposing students to a breadth of structural characterization techniques that broaden their learning experience.