On the origin of shape fluctuations of the cell nucleus

The nuclear envelope (NE) presents a physical boundary between the cytoplasm and the nucleoplasm, sandwiched in between two highly active systems inside the cell: cytoskeleton and chromatin. NE defines the shape and size of the cell nucleus, which increases during the cell cycle, accommodating for c...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 114; no. 39; pp. 10338 - 10343
Main Authors Chu, Fang-Yi, Haley, Shannon C., Zidovska, Alexandra
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 26.09.2017
Subjects
Cell cycle
Cell size
Chromatin
Confocal microscopy
Cytoplasm
Cytoskeleton
Fluctuations
Gene expression
Gene regulation
Genomes
Histone H2B
Microscopy
Nuclear pores
Nuclear transport
Nuclei (cytology)
Physical Sciences
nuclear envelope
nuclear lamina
active materials
chromatin
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Summary:The nuclear envelope (NE) presents a physical boundary between the cytoplasm and the nucleoplasm, sandwiched in between two highly active systems inside the cell: cytoskeleton and chromatin. NE defines the shape and size of the cell nucleus, which increases during the cell cycle, accommodating for chromosome decondensation followed by genome duplication. In this work, we study nuclear shape fluctuations at short time scales of seconds in human cells. Using spinning disk confocal microscopy,weobserve fast fluctuations of the NE, visualized by fluorescently labeled lamin A, and of the chromatin globule surface (CGS) underneath the NE, visualized by fluorescently labeled histone H2B. Our findings reveal that fluctuation amplitudes of both CGS and NE monotonously decrease during the cell cycle, serving as a reliable cell cycle stage indicator. Remarkably, we find that, while CGS and NE typically fluctuate in phase, they do exhibit localized regions of out-of-phase motion, which lead to separation of NE and CGS. To explore the mechanism behind these shape fluctuations, we use biochemical perturbations. We find the shape fluctuations of CGS and NE to be both thermally and actively driven, the latter caused by forces from chromatin and cytoskeleton. Such undulations might affect gene regulation as well as contribute to the anomalously high rates of nuclear transport by, e.g., stirring of molecules next to NE, or increasing flux of molecules through the nuclear pores.
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Edited by David A. Weitz, Harvard University, Cambridge, MA, and approved August 15, 2017 (received for review February 10, 2017)
Author contributions: A.Z. designed research; F.-Y.C. and A.Z. performed research; F.-Y.C., S.C.H., and A.Z. contributed new reagents/analytic tools; F.-Y.C. and A.Z. analyzed data; and F.-Y.C. and A.Z. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1702226114