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

Autor: Greta M. Bauer, Aya Eid, John F. Marko, Luay M. Almassalha, Hariharan Subramanian, Simona Morochnik, Di Zhang, Wenli Wu, John E. Chandler, Guillermo A. Ameer, Scott Gladstein, Vadim Backman, Andrew D. Stephens, Igal Szleifer, Adam Eshein, Lusik Cherkezyan
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019)
Nature Communications
ISSN: 2041-1723
Popis: 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.
Methods to track molecular motion in eukaryotic cells mostly rely on fluorescent labels, transfection or photobleaching. Here the authors use multimodal partial wave spectroscopy to perform label-free live cell measurements of nanoscale structure and macromolecular motion with millisecond temporal resolution.
Databáze: OpenAIRE