Mechanics and functional consequences of nuclear deformations

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(9), С. 583 - 602

Опубликована: Май 5, 2022

Язык: Английский

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Physical properties of the cytoplasm modulate the rates of microtubule polymerization and depolymerization

Developmental Cell, Год журнала: 2022, Номер 57(4), С. 466 - 479.e6

Опубликована: Фев. 1, 2022

The cytoplasm is a crowded, visco-elastic environment whose physical properties change according to physiological or developmental states. How the of impact cellular functions in vivo remains poorly understood. Here, we probe effects cytoplasmic concentration on microtubules by applying osmotic shifts fission yeast, moss, and mammalian cells. We show that rates both microtubule polymerization depolymerization scale linearly inversely with concentration; an increase decreases proportionally, whereas decrease leads opposite. Numerous lines evidence indicate these are due changes viscosity rather than stress responses macromolecular crowding per se. reconstituted vitro tuning viscosity. Our findings that, even normal conditions, modulates reactions underlie dynamic behaviors.

Язык: Английский

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Balance of osmotic pressures determines the nuclear-to-cytoplasmic volume ratio of the cell

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(21)

Опубликована: Май 17, 2022

The volume of the cell nucleus varies across types and species is commonly thought to be determined by size genome degree chromatin compaction. However, this notion has been challenged over years much experimental evidence. Here, we consider physical condition mechanical force balance as a determining nuclear use quantitative, order-of-magnitude analysis estimate forces from different sources cytoplasmic pressure. Our estimates suggest that dominant pressure within cytoplasm nonstriated muscle cells originates osmotic proteins RNA molecules are localized or out-of-equilibrium, active nucleocytoplasmic transport rather than its associated ions. This motivates us formulate model for ratio volumes in which pressures determine relative volumes. In accordance with unexplained observations century old, our predicts constant, robust wide variety biochemical biophysical manipulations, changed only if gene expression modulated.

Язык: Английский

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Physical basis of the cell size scaling laws

eLife, Год журнала: 2023, Номер 12

Опубликована: Май 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.

Язык: Английский

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Vast heterogeneity in cytoplasmic diffusion rates revealed by nanorheology and Doppelgänger simulations

Biophysical Journal, Год журнала: 2023, Номер 122(5), С. 767 - 783

Опубликована: Фев. 3, 2023

The cytoplasm is a complex, crowded, actively driven environment whose biophysical characteristics modulate critical cellular processes such as cytoskeletal dynamics, phase separation, and stem cell fate. Little known about the variance in these cytoplasmic properties. Here, we employed particle-tracking nanorheology on genetically encoded multimeric 40 nm nanoparticles (GEMs) to measure diffusion within of individual fission yeast (Schizosaccharomyces pombe) cellscells. We found that apparent coefficients GEM particles varied over 400-fold range, while differences average particle diffusivity among cells spanned 10-fold range. To determine origin this heterogeneity, developed Doppelgänger simulation approach uses stochastic simulations replicate experimental statistics particle-by-particle basis, each track had one-to-one correspondence with their simulated counterpart. These showed large intra- inter-cellular variations could not be explained by variability but only reproduced models assume wide variation viscosity. combining viscosity also predicted weak nonergodicity diffusion, consistent data. probe variation, was largely independent factors temperature, actin microtubule cytoskeletons, cell-cyle stage, spatial locations, magnified hyperosmotic shocks. Taken together, our results provide striking demonstration "well-mixed" represents highly heterogeneous which subcellular components at size scale experience dramatically different effective viscosities an cell, well identical population. findings carry significant implications for origins regulation biological noise levels.

Язык: Английский

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

Developmental Cell, Год журнала: 2023, Номер 58(16), С. 1462 - 1476.e8

Опубликована: Июнь 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.

Язык: Английский

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Size- and position-dependent cytoplasm viscoelasticity through hydrodynamic interactions with the cell surface

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(9)

Опубликована: Фев. 21, 2023

Many studies of cytoplasm rheology have focused on small components in the submicrometer scale. However, also baths large organelles like nuclei, microtubule asters, or spindles that often take significant portions cells and move across to regulate cell division polarization. Here, we translated passive sizes ranging from few up ~50 percents diameter, through vast live sea urchin eggs, with calibrated magnetic forces. Creep relaxation responses indicate for objects larger than micron size, behaves as a Jeffreys material, viscoelastic at short timescales, fluidizing longer times. component size approached cells, resistance increased nonmonotonic manner. Flow analysis simulations suggest this size-dependent viscoelasticity emerges hydrodynamic interactions between moving object static surface. This effect yields position-dependent initially closer surface being harder displace. These findings hydrodynamically couples restrain their motion, important implications shape sensing cellular organization.

Язык: Английский

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Nuclear pores as conduits for fluid flow during osmotic stress

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 17, 2024

Abstract Changing environmental conditions necessitate an immediate cellular adaptation to ensure survival. Dictyostelium discoideum , a bacteriovore slime mold present in the soil of most terrestrial ecosystems, is known for its ability tolerate drastic changes osmolarity. How cells cope with resulting mechanical stress remains understudied. Here we show that D. has extraordinarily elaborate and resilient nuclear pores serve as conduits massive fluid exchange between cytosol nucleus. We capitalize on unique properties quantify flow across envelope necessitated by changing size response osmotic stress. Based mathematical concepts adapted from hydrodynamics, conceptualize this phenomenon porous pores. This type distinct canonically characterized modes nucleocytoplasmic transport, i.e. passive diffusion active because dependence pressure. Our insights are relevant any biological condition necessitates rapid changes, which includes metastasizing cancer squeezing through constrictions, migrating differentiating tissues.

Язык: Английский

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The Nuclear-to-Cytoplasmic Ratio: Coupling DNA Content to Cell Size, Cell Cycle, and Biosynthetic Capacity

Annual Review of Genetics, Год журнала: 2022, Номер 56(1), С. 165 - 185

Опубликована: Авг. 17, 2022

Though cell size varies between different cells and across species, the nuclear-to-cytoplasmic (N/C) ratio is largely maintained species within types. A maintains a relatively constant N/C by coupling DNA content, nuclear size, size. We explore how couple division growth to content. In some cases, use as molecular yardstick control availability of cycle regulators. other sets limit for biosynthetic capacity. Developmentally programmed variations in given type suggest that specific required respond physiological demands. Recent observations connecting decreased ratios with cellular senescence indicate maintaining proper essential functioning. Together, these findings causative, not simply correlative, role regulating progression.

Язык: Английский

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

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Окт. 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.

Язык: Английский

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