1. Advancing High-Resolution Imaging of Virus Assemblies in Liquid and Ice
- Author
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Deborah F. Kelly, Sarah M. McDonald Esstman, Kathryn Grandfield, Madeline J. Dressel-Dukes, Michael Spilman, William J. Dearnaley, Carol Bator, Jennifer L. Gray, Liam Kaylor, Maria J. Solares, G. M. Jonaid, Samantha Berry, and Liza-Anastasia DiCecco
- Subjects
General Immunology and Microbiology ,SARS-CoV-2 ,General Chemical Engineering ,General Neuroscience ,Cryoelectron Microscopy ,Ice ,COVID-19 ,Humans ,General Biochemistry, Genetics and Molecular Biology ,Specimen Handling - Abstract
Interest in liquid-electron microscopy (liquid-EM) has skyrocketed in recent years as scientists can now observe real-time processes at the nanoscale. It is extremely desirable to pair high-resolution cryo-EM information with dynamic observations as many events occur at rapid timescales - in the millisecond range or faster. Improved knowledge of flexible structures can also assist in the design of novel reagents to combat emerging pathogens, such as SARS-CoV-2. More importantly, viewing biological materials in a fluid environment provides a unique glimpse of their performance in the human body. Presented here are newly developed methods to investigate the nanoscale properties of virus assemblies in liquid and vitreous ice. To accomplish this goal, well-defined samples were used as model systems. Side-by-side comparisons of sample preparation methods and representative structural information are presented. Sub-nanometer features are shown for structures resolved in the range of ~3.5-Å-10 Å. Other recent results that support this complementary framework include dynamic insights of vaccine candidates and antibody-based therapies imaged in liquid. Overall, these correlative applications advance our ability to visualize molecular dynamics, providing a unique context for their use in human health and disease.
- Published
- 2022