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

Scott Gladstein, Luay M. Almassalha, Lusik Cherkezyan, John E. Chandler, Adam Eshein, Aya Eid, Di Zhang, Wenli Wu, Greta M. Bauer, Andrew D. Stephens, Simona Morochnik, Hariharan Subramanian, John F. Marko, Guillermo A. Ameer, Igal Szleifer and Vadim Backman ()
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Scott Gladstein: Northwestern University
Luay M. Almassalha: Northwestern University
Lusik Cherkezyan: Northwestern University
John E. Chandler: Northwestern University
Adam Eshein: Northwestern University
Aya Eid: Northwestern University
Di Zhang: Northwestern University
Wenli Wu: Northwestern University
Greta M. Bauer: Northwestern University
Andrew D. Stephens: Northwestern University
Simona Morochnik: Northwestern University
Hariharan Subramanian: Northwestern University
John F. Marko: Northwestern University
Guillermo A. Ameer: Northwestern University
Igal Szleifer: Northwestern University
Vadim Backman: Northwestern University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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 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.

Date: 2019
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DOI: 10.1038/s41467-019-09717-6

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