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Cryo‐EM‐On‐a‐Chip: Custom‐Designed Substrates for the 3D Analysis of Macromolecules
Author(s) -
Alden Nick A.,
Varano A. Cameron,
Dearnaley William J.,
Solares Maria J.,
Luqiu William Y.,
Liang Yanping,
Sheng Zhi,
McDonald Sarah M.,
Damiano John,
McConnell Jennifer,
Dukes Madeline J.,
Kelly Deborah F.
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201900918
Subject(s) - nanotechnology , macromolecule , computational biology , glioblastoma , function (biology) , dna , suppressor , computer science , materials science , cancer , biology , microbiology and biotechnology , cancer research , biochemistry , genetics
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.