Mechanics and functional consequences of nuclear deformations

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(9), P. 583 - 602

Published: May 5, 2022

Language: Английский

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Cell Growth and Division

Oxford University Press eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 191 - 224

Published: Feb. 29, 2024

Abstract Numerous correlates of cell growth are thought to be general enough christened as laws, although few have been examined thoroughly in multiple organisms. One well-established relationship is the linear increase ribosome number with cell-division rate, which reflects necessity ribosomes for construction cellular material. Cell division rates a hyperbolic concentrations limiting nutrients. The individual cells generally exponential, cytosolic compositions remaining constant throughout growth. Cells often determine their times by waiting critical increments growth, naturally results cell-size homeostasis. Although detailed molecular mechanisms governing these kinds behavior unknown, modifications small genes implicated potential routes evolution. In all observed species, whereas size increases nutrient availability, it decreases increasing temperature, driving universal responses remain unknown. Despite features stochastic sources internal variation translate into considerable phenotypic among genetically identical cells. Such can obscure visibility genetic differences natural selection, while also leading parent–offspring similarity associated non-genetic effects. These aspects inheritance inevitable consequences structure cells, and there no evidence that high levels advanced selection means coping variable environments.

Language: Английский

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Lamins: The backbone of the nucleocytoskeleton interface

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 86, P. 102313 - 102313

Published: Jan. 22, 2024

Language: Английский

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Control of nuclear size by osmotic forces in Schizosaccharomyces pombe

eLife, Journal Year: 2022, Volume and Issue: 11

Published: July 20, 2022

The size of the nucleus scales robustly with cell so that nuclear-to-cell volume ratio (N/C ratio) is maintained during growth in many types. mechanism responsible for this scaling remains mysterious. Previous studies have established N/C not determined by DNA amount but instead influenced factors such as nuclear envelope mechanics and transport. Here, we developed a quantitative model control based upon colloid osmotic pressure tested key predictions fission yeast Schizosaccharomyces pombe . This posits numbers macromolecules nucleoplasm cytoplasm. Osmotic shift experiments showed behaves an ideal osmometer whose primarily dictated forces. Inhibition export caused accumulation nucleoplasm, leading to swelling. We further demonstrated homeostasis synthesis growth. These demonstrate functions intracellular organization control.

Language: Английский

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Physical basis of the cell size scaling laws

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 2, 2023

Cellular growth is the result of passive physical constraints and active biological processes. Their interplay leads to appearance robust ubiquitous scaling laws relating linearly cell size, dry mass, nuclear size. Despite accumulating experimental evidence, their origin still unclear. Here, we show that these can be explained quantitatively by a single model size regulation based on three simple, yet generic, defining altogether Pump-Leak model. Based quantitative estimates, clearly map coarse-grained parameters with dominant cellular components. We propose mass density homeostasis arises from between proteins small osmolytes, mainly amino acids ions. Our predicts this naturally fail, both at senescence when DNA RNAs are saturated RNA polymerases ribosomes, respectively, mitotic entry due counterion release following histone tail modifications. same laws, further results osmotic balance envelope large pool metabolites, which dilutes chromatin counterions do not scale during growth.

Language: Английский

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Epithelial tissue confinement inhibits cell growth and leads to volume-reducing divisions

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(16), P. 1462 - 1476.e8

Published: June 19, 2023

Cell proliferation is a central process in tissue development, homeostasis, and disease, yet how regulated the context remains poorly understood. Here, we introduce quantitative framework to elucidate growth dynamics regulate cell proliferation. Using MDCK epithelial monolayers, show that limiting rate of expansion creates confinement suppresses growth; however, this does not directly affect cycle. This leads uncoupling between rates division epithelia and, thereby, reduces volume. Division becomes arrested at minimal volume, which consistent across diverse vivo. nucleus approaches minimum volume capable packaging genome. Loss cyclin D1-dependent cell-volume regulation results an abnormally high nuclear-to-cytoplasmic ratio DNA damage. Overall, demonstrate by interplay regulation.

Language: Английский

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Regulation of chromatin microphase separation by binding of protein complexes

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 12, 2023

We show evidence of the association RNA polymerase II (RNAP) with chromatin in a core-shell organization, reminiscent microphase separation where cores comprise dense and shell, RNAP low density. These observations motivate our physical model for regulation organization. Here, we as multiblock copolymer, comprising active inactive regions (blocks) that are both poor solvent tend to be condensed absence binding proteins. However, quality can regulated by protein complexes (e.g., transcription factors). Using theory polymer brushes, find such leads swelling which turn modifies spatial organization regions. In addition, use simulations study spherical micelles, whose shells bound complexes. micelles increases number controls their size. Thus, genetic modifications affecting strength chromatin-binding may modulate experienced regulate genome.

Language: Английский

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The uniformity and stability of cellular mass density in mammalian cell culture

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 12, 2022

Cell dry mass is principally determined by the sum of biosynthesis and degradation. Measurable change in occurs on a time scale hours. By contrast, cell volume can minutes altering osmotic conditions. How changes are coupled fundamental question size control. If were proportional to during growth, would always maintain same cellular density, defined as dividing volume. The accuracy stability against perturbation this proportionality has never been stringently tested. Normalized Raman Imaging (NoRI), measure both protein lipid density directly . Using new technique , we have able investigate response pharmaceutical physiological perturbations three cultured mammalian lines. We find remarkably narrow distribution within cells, that is, significantly tighter than variability or distribution. measured independent cycle. be modulated extracellular osmolytes disruptions cytoskeleton. Yet, surprisingly resistant pharmacological synthesis degradation, suggesting there must some form feedback control homeostasis when altered. such starvation senescence induce significant shifts density. begun shed light how why remains fixed yet sensitive transitions state.

Language: Английский

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3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen Encephalitozoon intestinalis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 23, 2023

Abstract Microsporidia are an early-diverging group of fungal pathogens with a wide host range. Several microsporidian species cause opportunistic infections in humans that can be fatal. As obligate intracellular parasites highly reduced genomes, microsporidia dependent on metabolites for successful replication and development. Our knowledge development remains rudimentary, our understanding the niche occupied by has relied 2D TEM images light microscopy. Here, we use serial block-face scanning electron microscopy (SBF-SEM) to capture 3D snapshots human-infecting species, Encephalitozoon intestinalis , within cells. We track E. through its life cycle, which allows us propose model how infection organelle, polar tube, is assembled de novo developing spores. reconstructions parasite-infected cells provide insights into physical interactions between cell organelles parasitophorous vacuoles, contain parasites. The mitochondrial network substantially remodeled during infection, leading fragmentation. SBF-SEM analysis shows changes morphology infected cells, live-cell imaging provides dynamics infection. data parasite development, tube assembly, microsporidia-induced mitochondria remodeling.

Language: Английский

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Scaling behaviour and control of nuclear wrinkling

Nature Physics, Journal Year: 2023, Volume and Issue: 19(12), P. 1927 - 1935

Published: Sept. 18, 2023

Language: Английский

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