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; Vadim Backman

doi:10.1038/s41467-019-09717-6

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, Vadim Backman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Article number	1652
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-09717-6
State	Published - Dec 1 2019

Funding

This work was supported by fellowships and grants from the National Institutes of Health grant R01-GM105847, R01 CA200064, R33CA225323, 1R01CA228272, R01CA225002, R01EB016983, R01CA165309, K99 GM123195, the National Cancer Institute grant U54-CA193419 (CR-PS-OC), the NIH Chemistry of Life Processes Predoctoral Training grant #5T32GM105538-03 and the National Science Foundation grant CBET-1240416. An award of computer time was provided by the INCITE program. This research used resources of the Argonne Leadership Computing Facility, which is a DOE Office of Science User Facility supported under Contract DE-AC02-06CH11357.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Gladstein, S., Almassalha, L. M., Cherkezyan, L., Chandler, J. E., Eshein, A., Eid, A., Zhang, D., Wu, W., Bauer, G. M., Stephens, A. D., Morochnik, S., Subramanian, H., Marko, J. F., Ameer, G. A., Szleifer, I., & Backman, V. (2019). Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm. Nature communications, 10(1), Article 1652. https://doi.org/10.1038/s41467-019-09717-6

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

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.",

author = "Scott Gladstein and Almassalha, {Luay M.} and Lusik Cherkezyan and Chandler, {John E.} and Adam Eshein and Aya Eid and Di Zhang and Wenli Wu and Bauer, {Greta M.} and Stephens, {Andrew D.} and Simona Morochnik and Hariharan Subramanian and Marko, {John F.} and Ameer, {Guillermo A.} and Igal Szleifer and Vadim Backman",

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Gladstein, S, Almassalha, LM, Cherkezyan, L, Chandler, JE, Eshein, A, Eid, A, Zhang, D, Wu, W, Bauer, GM, Stephens, AD, Morochnik, S, Subramanian, H, Marko, JF , Ameer, GA , Szleifer, I & Backman, V 2019, 'Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm', Nature communications, vol. 10, no. 1, 1652. https://doi.org/10.1038/s41467-019-09717-6

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AU - Almassalha, Luay M.

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AU - Eshein, Adam

AU - Eid, Aya

AU - Zhang, Di

AU - Wu, Wenli

AU - Bauer, Greta M.

AU - Stephens, Andrew D.

AU - Morochnik, Simona

AU - Subramanian, Hariharan

AU - Marko, John F.

AU - Ameer, Guillermo A.

AU - Szleifer, Igal

AU - Backman, Vadim

PY - 2019/12/1

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N2 - 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.

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

Abstract

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