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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number1900918
JournalSmall
Volume15
Issue number21
DOIs
StatePublished - May 24 2019

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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