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journal article·2019-05Open access

Cryo‐EM‐On‐a‐Chip: Custom‐Designed Substrates for the 3D Analysis of Macromolecules

Nick A. Alden, A. Cameron Varano, William J. Dearnaley, Maria J. Solares, William Y. Luqiu, Yanping Liang, Zhi Sheng, Sarah M. McDonald, John Damiano, Jennifer McConnell, Madeline J. Dukes, Deborah F. Kelly

Small· Volume 15· Issue 21
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Abstract

Abstract The fight against human disease requires a multidisciplinary scientific approach. Applying tools from seemingly unrelated areas, such as materials science and molecular biology, researchers can overcome long‐standing challenges to improve knowledge of molecular pathologies. Here, custom‐designed substrates composed of silicon nitride (SiN) are used to study the 3D attributes of tumor suppressor proteins that function in DNA repair events. New on‐chip preparation strategies enable the isolation of native protein complexes from human cancer cells. Combined techniques of cryo‐electron microscopy (EM) and molecular modeling reveal a new modified form of the p53 tumor suppressor present in aggressive glioblastoma multiforme cancer cells. Taken together, the findings provide a radical new design for cryo‐EM substrates to evaluate the structures of disease‐related macromolecules.
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Research context

Polymers

OpenAlex topics: Advanced Electron Microscopy Techniques and Applications · Electron and X-Ray Spectroscopy Techniques · Advanced biosensing and bioanalysis techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Virginia Tech Carilion Research Institute Virginia Tech Roanoke VA 24016 USA

Department of Biomedical Engineering Pennsylvania State University University Park PA 16802 USA

Center for Structural Oncology Pennsylvania State University University Park PA 16802 USA

Translational Biology Medicine, and Health Graduate Program Virginia Tech Blacksburg VA 24061 USA

Huck Institutes of the Life Sciences Pennsylvania State University University Park PA 16802 USA

Department of Biology Wake Forest University Winston‐Salem NC 27109 USA

Application Science Protochips Inc. Morrisville NC 27560 USA

Funding

National Institutes of Health

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