Multimodal interferometric 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:10.1101/428383

Multimodal interferometric 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

Abstract

We present a multimodal label-free interferometric imaging platform for measuring intracellular nanoscale structure and macromolecular dynamics in living cells with a sensitivity to macromolecules as small as 20nm and millisecond temporal resolution. We validate this system by pairing experimental measurements of nanosphere phantoms with a novel interferometric theory. Applying this system in vitro, we explore changes in higher-order chromatin structure and dynamics that occur due to cellular fixation, stem cell differentiation, and ultraviolet (UV) light irradiation. Finally, we discover a new phenomenon, cellular paroxysm, a near-instantaneous, synchronous burst of motion that occurs early in the process of UV induced cell death. Given this platform’s ability to obtain nanoscale sensitive, millisecond resolved information within live cells without concerns of photobleaching, it has the potential to answer a broad range of critical biological questions about macromolecular behavior in live cells, particularly about the relationship between cellular structure and function.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/428383
State	Published - Oct 1 2018

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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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. (2018). Multimodal interferometric imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm. Unknown Journal. https://doi.org/10.1101/428383

Gladstein, Scott ; Almassalha, Luay M. ; Cherkezyan, Lusik ; Chandler, John E. ; Eshein, Adam ; Eid, Aya ; Zhang, Di ; Wu, Wenli ; Bauer, Greta M. ; Stephens, Andrew D. ; Morochnik, Simona ; Subramanian, Hariharan ; Marko, John F. ; Ameer, Guillermo A. ; Szleifer, Igal ; Backman, Vadim. / Multimodal interferometric imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm. In: Unknown Journal. 2018.

@article{43a5514d79ba4ce28d39a02ac65b0806,

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

abstract = "We present a multimodal label-free interferometric imaging platform for measuring intracellular nanoscale structure and macromolecular dynamics in living cells with a sensitivity to macromolecules as small as 20nm and millisecond temporal resolution. We validate this system by pairing experimental measurements of nanosphere phantoms with a novel interferometric theory. Applying this system in vitro, we explore changes in higher-order chromatin structure and dynamics that occur due to cellular fixation, stem cell differentiation, and ultraviolet (UV) light irradiation. Finally, we discover a new phenomenon, cellular paroxysm, a near-instantaneous, synchronous burst of motion that occurs early in the process of UV induced cell death. Given this platform{\textquoteright}s ability to obtain nanoscale sensitive, millisecond resolved information within live cells without concerns of photobleaching, it has the potential to answer a broad range of critical biological questions about macromolecular behavior in live cells, particularly about the relationship between cellular structure and function.",

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",

note = "Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2018",

month = oct,

day = "1",

doi = "10.1101/428383",

language = "English (US)",

journal = "Free Radical Biology and Medicine",

issn = "0891-5849",

publisher = "Elsevier Inc.",

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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 2018, 'Multimodal interferometric imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm', Unknown Journal. https://doi.org/10.1101/428383

Multimodal interferometric imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm. / Gladstein, Scott; Almassalha, Luay M.; Cherkezyan, Lusik; Chandler, John E.; Eshein, Adam; Eid, Aya; Zhang, Di; Wu, Wenli; Bauer, Greta M.; Stephens, Andrew D.; Morochnik, Simona; Subramanian, Hariharan ; Marko, John F.; Ameer, Guillermo A.; Szleifer, Igal ; Backman, Vadim.

In: Unknown Journal, 01.10.2018.

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

TY - JOUR

T1 - Multimodal interferometric imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm

AU - Gladstein, Scott

AU - Almassalha, Luay M.

AU - Cherkezyan, Lusik

AU - Chandler, John E.

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

N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - We present a multimodal label-free interferometric imaging platform for measuring intracellular nanoscale structure and macromolecular dynamics in living cells with a sensitivity to macromolecules as small as 20nm and millisecond temporal resolution. We validate this system by pairing experimental measurements of nanosphere phantoms with a novel interferometric theory. Applying this system in vitro, we explore changes in higher-order chromatin structure and dynamics that occur due to cellular fixation, stem cell differentiation, and ultraviolet (UV) light irradiation. Finally, we discover a new phenomenon, cellular paroxysm, a near-instantaneous, synchronous burst of motion that occurs early in the process of UV induced cell death. Given this platform’s ability to obtain nanoscale sensitive, millisecond resolved information within live cells without concerns of photobleaching, it has the potential to answer a broad range of critical biological questions about macromolecular behavior in live cells, particularly about the relationship between cellular structure and function.

AB - We present a multimodal label-free interferometric imaging platform for measuring intracellular nanoscale structure and macromolecular dynamics in living cells with a sensitivity to macromolecules as small as 20nm and millisecond temporal resolution. We validate this system by pairing experimental measurements of nanosphere phantoms with a novel interferometric theory. Applying this system in vitro, we explore changes in higher-order chromatin structure and dynamics that occur due to cellular fixation, stem cell differentiation, and ultraviolet (UV) light irradiation. Finally, we discover a new phenomenon, cellular paroxysm, a near-instantaneous, synchronous burst of motion that occurs early in the process of UV induced cell death. Given this platform’s ability to obtain nanoscale sensitive, millisecond resolved information within live cells without concerns of photobleaching, it has the potential to answer a broad range of critical biological questions about macromolecular behavior in live cells, particularly about the relationship between cellular structure and function.

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DO - 10.1101/428383

M3 - Article

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