Gene expression in growing cells: A biophysical primer DOI Creative Commons
Ido Golding, Ariel Amir

arXiv (Cornell University), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Cell growth and gene expression, essential elements of all living systems, have long been the focus biophysical interrogation. Advances in single-cell methods invigorated theoretical studies into these processes. However, until recently, there was little dialog between two areas study. Most models for regulation assumed activity to be oblivious progression cell cycle birth division. But are numerous ways which periodic character cellular observables can modulate expression. The molecular factors required transcription translation increase number during cycle, but also diluted due continuous volume. replication genome changes dosage those same players provides competing targets regulatory binding. Finally, division reduces their again, so forth. Stochasticity is inherent biological processes, manifested fluctuations synthesis degradation new components as well random partitioning molecules at each notion expression stationary thus hard justify. In this review, we survey emerging paradigm cell-cycle regulated with an emphasis on global patterns rather than gene-specific regulation. We discuss recent experimental reports where were simultaneously measured individual cells, providing first glimpses coupling two. While findings, not surprisingly, differ among genes organisms, several emerged that attempt reconcile differences form a unifying framework understanding growing cells.

Language: Английский

Metabolic regulation of species-specific developmental rates DOI
Margarete Díaz-Cuadros, Teemu P. Miettinen, Owen S. Skinner

et al.

Nature, Journal Year: 2023, Volume and Issue: 613(7944), P. 550 - 557

Published: Jan. 4, 2023

Language: Английский

Citations

95
A mechano-osmotic feedback couples cell volume to the rate of cell deformation DOI Creative Commons
Larisa Venkova, Amit Singh Vishen, Sergio Lembo

et al.

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

Published: April 13, 2022

Mechanics has been a central focus of physical biology in the past decade. In comparison, how cells manage their size is less understood. Here, we show that parameter to both physics and physiology cell, its volume, depends on mechano-osmotic coupling. We found change volume depending rate at which they shape, when spontaneously spread or are externally deformed. Cells undergo slow deformation constant while fast leads loss. propose mechanosensitive pump leak model explain this phenomenon. Our experiments suggest modulation state actin cortex coupling ion fluxes membrane tension. This defines tension homeostasis module constantly work cells, causing fluctuations associated with cell shape changes, potential consequences cellular physiology.

Language: Английский

Citations

60
Epithelial tissue confinement inhibits cell growth and leads to volume-reducing divisions DOI Creative Commons
John Devany,

Martin J. Falk,

Liam J. Holt

et al.

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

Citations

27
The Nuclear-to-Cytoplasmic Ratio: Coupling DNA Content to Cell Size, Cell Cycle, and Biosynthetic Capacity DOI Open Access

Shruthi Balachandra,

Sharanya Sarkar, Amanda A. Amodeo

et al.

Annual Review of Genetics, Journal Year: 2022, Volume and Issue: 56(1), P. 165 - 185

Published: Aug. 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.

Language: Английский

Citations

37
The uniformity and stability of cellular mass density in mammalian cell culture DOI Creative Commons
Xili Liu, Seungeun Oh, Marc W. Kirschner

et al.

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

Citations

31
Temporal segregation of biosynthetic processes is responsible for metabolic oscillations during the budding yeast cell cycle DOI Creative Commons
Vakil Takhaveev,

Serdar Özsezen,

Edward Smith

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(2), P. 294 - 313

Published: Feb. 27, 2023

Many cell biological and biochemical mechanisms controlling the fundamental process of eukaryotic division have been identified; however, temporal dynamics biosynthetic processes during cycle are still elusive. Here, we show that key temporally segregated along cycle. Using budding yeast as a model single-cell methods to dynamically measure metabolic activity, observe two peaks in protein synthesis, G1 S/G2/M phase, whereas lipid polysaccharide synthesis only once, phase. Integrating inferred rates into thermodynamic-stoichiometric model, find this segregation causes flux changes primary metabolism, with an acceleration glucose-uptake phase-shifted oscillations oxygen carbon dioxide exchanges. Through experimental validation predictions, demonstrate metabolism oscillates cell-cycle periodicity satisfy changing demands exhibiting unexpected

Language: Английский

Citations

21
Scaling of biosynthesis and metabolism with cell size DOI
Clotilde Cadart, Rebecca Heald

Molecular Biology of the Cell, Journal Year: 2022, Volume and Issue: 33(9)

Published: Aug. 1, 2022

Cells adopt a size that is optimal for their function, and pushing them beyond this limit can cause cell aging death by senescence or reduce proliferative potential. However, increasing genome copy number (ploidy), cells increase dramatically homeostatically maintain physiological properties such as biosynthesis rate. Recent studies investigating the relationship between rates of metabolism under normal, polyploid, pathological conditions are revealing new insights into how attain best function fitness tuning processes including transcription, translation, mitochondrial respiration. A frontier to connect single-cell scaling relationships with tissue whole-organism physiology, which promises reveal molecular evolutionary principles underlying astonishing diversity observed across tree life.

Language: Английский

Citations

25
Measuring single-cell density with high throughput enables dynamic profiling of immune cell and drug response from patient samples DOI
Weida Wu, Sarah H. Ishamuddin,

Thomas W Quinn

et al.

Published: April 28, 2024

Cell density, the ratio of cell mass to volume, is an indicator molecular crowding and therefore a fundamental determinant state function. However, existing density measurements lack precision or throughput quantify subtle differences in states, particularly primary samples. Here we present approach for measuring 30,000 single cells per hour with 0.03% (0.0003 g/mL) by integrating fluorescence exclusion microscopy suspended microchannel resonator. Applying this human lymphocytes, discovered that its variation decrease as transition from quiescence proliferative state, suggesting level decreases becomes more regulated upon entry into cycle. Using pancreatic cancer patient-derived xenograft model, found ex vivo response tumor drug treatment can predict growth response. Our method reveals unexpected behavior during transitions suggests new biomarker functional medicine.

Language: Английский

Citations

6
Eukaryotic cell size regulation and its implications for cellular function and dysfunction DOI
Yagya Chadha, Arohi Khurana, Kurt M. Schmoller

et al.

Physiological Reviews, Journal Year: 2024, Volume and Issue: 104(4), P. 1679 - 1717

Published: June 20, 2024

Depending on cell type, environmental inputs, and disease, the cells in human body can have widely different sizes. In recent years, it has become clear that size is a major regulator of function. However, we are only beginning to understand how optimization function determines given cell’s optimal size. Here, review currently known control strategies eukaryotic intricate link intracellular biomolecular scaling, organelle homeostasis, cycle progression. We detail size-dependent regulation early development impact differentiation. Given importance for normal cellular physiology, must account changing conditions. describe sense stimuli, such as nutrient availability, accordingly adapt their by regulating growth Moreover, discuss correlation pathological states with misregulation long time this was considered downstream consequence dysfunction. newer studies reveal reversed causality, misregulated leading pathophysiological phenotypes senescence aging. summary, highlight important roles dysfunction, which could implications both diagnostics treatment clinic.

Language: Английский

Citations

6
Cell-intrinsic mechanical regulation of plasma membrane accumulation at the cytokinetic furrow DOI Creative Commons
Roberto Alonso‐Matilla, Alice Lam, Teemu P. Miettinen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(29)

Published: July 11, 2024

Cytokinesis is the process where mother cell’s cytoplasm separates into daughter cells. This driven by an actomyosin contractile ring that produces cortical contractility and drives cleavage furrow ingression, resulting in formation of a thin intercellular bridge. While cytoskeletal reorganization during cytokinesis has been extensively studied, less known about spatiotemporal dynamics plasma membrane. Here, we image model membrane lipid protein on cell surface leukemia cytokinesis. We reveal extensive accumulation folding at bridge, accompanied depletion unfolding poles. These are caused two actomyosin-driven biophysical mechanisms: radial constriction causes local compression apparent area furrow, while flows drag toward division plane as ingresses. The magnitude these effects depends fluidity, cortex adhesion, contractility. Overall, our work reveals cell-intrinsic mechanical regulation likely to generate localized differences tension across cytokinetic cell. may locally alter endocytosis, exocytosis, mechanotransduction, also serving self-protecting mechanism against failures arise from high

Language: Английский

Citations

6