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Title: Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm

Journal Article · · Nature Communications
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [1];  [3];  [4];  [5];  [5];  [5]
  1. Northwestern Univ., Evanston, IL (United States). Dept. of Biomedical Engineering
  2. Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences
  3. Northwestern Univ., Evanston, IL (United States). Dept. of Biomedical Engineering; Northwestern Univ., Evanston, IL (United States). Center for Advanced Regenerative Engineering
  4. Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences; Northwestern Univ., Evanston, IL (United States). Dept. of Physics & Astronomy; Northwestern Univ., Evanston, IL (United States). Center for Physical Genomics and Engineering
  5. Northwestern Univ., Evanston, IL (United States). Dept. of Biomedical Engineering; Northwestern Univ., Evanston, IL (United States). Center for Advanced Regenerative Engineering; Northwestern Univ., Evanston, IL (United States). Center for Physical Genomics and Engineering
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Understanding the relationship between intracellular motion and macromolecular structure remains a challenge in biology. Macromolecular structures are assembled from numerous molecules, some of which cannot be labeled. Most techniques to study motion require potentially cytotoxic dyes or transfection, which can alter cellular behavior and are susceptible to photobleaching. Here in this paper, we present a multimodal label-free imaging platform for measuring intracellular structure and macromolecular dynamics in living cells with a sensitivity to macromolecular structure as small as 20 nm and millisecond temporal resolution. We develop and validate a theory for temporal measurements of light interference. In vitro, we study how higher-order chromatin structure and dynamics change during cell differentiation and ultraviolet (UV) light irradiation. Finally, we discover cellular paroxysms, a near-instantaneous burst of macromolecular motion that occurs during UV induced cell death. With nanoscale sensitive, millisecond resolved capabilities, this platform could address critical questions about macromolecular behavior in live cells.

Research Organization:
Univ. of California, Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Science Foundation (NSF)
Grant/Contract Number:
AC02-05CH11231; R01-GM105847; R01 CA200064; R33CA225323; 1R01CA228272; R01CA225002; R01EB016983; R01CA165309; K99 GM123195; CBET-1240416
OSTI ID:
1574387
Journal Information:
Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 8 works
Citation information provided by
Web of Science

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Disordered chromatin packing regulates phenotypic plasticity journal January 2020

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