Mechanical state transitions in the regulation of tissue form and function

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(8), P. 654 - 670

Published: April 10, 2024

Language: Английский

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Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology

Nature Nanotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Quantifying the mechanical response of biological milieu (such as cell’s interior) and complex fluids biomolecular condensates) would enable a better understanding cellular differentiation aging accelerate drug discovery. Here we present time-shared optical tweezer microrheology to determine frequency- age-dependent viscoelastic properties materials. Our approach involves splitting single laser beam into two near-instantaneous traps carry out simultaneous force displacement measurements quantify ranging from millipascals kilopascals across five decades frequency. To create practical robust nanorheometer, leverage both numerical analytical models analyse typical deviations ideal behaviour offer solutions account for these discrepancies. We demonstrate versatility technique by measuring liquid–solid phase transitions MEC-2 stomatin CPEB4 condensates, intracellular compartments zebrafish progenitor cells. In Caenorhabditis elegans , uncover how mutations in nuclear envelope proteins LMN-1 lamin A, EMR-1 emerin LEM-2 LEMD2, which cause premature disorders humans, soften cytosol intestinal cells during organismal age. that offers rapid phenotyping material inside protein blends, can be used biomedical drug-screening applications.

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

Biophysical Journal, Journal Year: 2023, Volume and Issue: 122(5), P. 767 - 783

Published: Feb. 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.

Language: Английский

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Synergistic effects of multiple rotors and hydrogen-bond interactions lead to sensitive near-infrared viscosity probes for live-cell microscopy

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(8), P. 2329 - 2338

Published: July 25, 2023

Language: Английский

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Microtubule-associated protein MAP7 promotes tubulin posttranslational modifications and cargo transport to enable osmotic adaptation

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(12), P. 1553 - 1570.e7

Published: April 3, 2024

Language: Английский

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An ultra high‐throughput, massively multiplexable, single‐cell RNA‐seq platform in yeasts

Yeast, Journal Year: 2024, Volume and Issue: 41(4), P. 242 - 255

Published: Jan. 28, 2024

Abstract Yeasts are naturally diverse, genetically tractable, and easy to grow such that researchers can investigate any number of genotypes, environments, or interactions thereof. However, studies yeast transcriptomes have been limited by the processing capabilities traditional RNA sequencing techniques. Here we optimize a powerful, high‐throughput single‐cell (scRNAseq) platform, SPLiT‐seq (Split Pool Ligation‐based Transcriptome sequencing), for yeasts apply it 43,388 cells multiple species ploidies. This platform utilizes combinatorial barcoding strategy enable massively parallel hundreds genotypes growth conditions at once. method be applied most strains fraction cost scRNAseq approaches. Thus, our technology permits leverage “the awesome power yeast” allowing us survey transcriptome environments in short period time with no specialized equipment. The key this is sequential barcodes probabilistically appended cDNA copies while molecules remain trapped inside each cell. cell labeled unique combination barcodes. Since uses membrane as container reaction, many processed together without need physically isolate them from one another separate wells droplets. Further, first barcode sequence chosen intentionally identify samples different genetic backgrounds, enabling multiplexing perturbations single experiment. In addition greater capabilities, also facilitates deeper investigation biological heterogeneity, given its nature. For example, data presented here, detect transcriptionally distinct states related cycle, ploidy, metabolic strategies, so forth, all within clonal populations grown same environment. Hence, has two obvious impactful applications research: general study transcriptional phenotypes across second investigating cell‐to‐cell heterogeneity entire transcriptome.

Language: 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, Journal Year: 2023, Volume and Issue: 120(9)

Published: Feb. 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.

Language: Английский

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Viscoelastic Multiscale Mechanical Indexes for Assessing Liver Fibrosis and Treatment Outcomes

Nano Letters, Journal Year: 2023, Volume and Issue: 23(20), P. 9618 - 9625

Published: Oct. 4, 2023

Understanding liver tissue mechanics, particularly in the context of pathologies like fibrosis, cirrhosis, and carcinoma, holds pivotal significance for assessing disease severity prognosis. Although static mechanical properties livers have been gradually studied, intricacies their dynamic mechanics remain enigmatic. Here, we characterize creep responses healthy, fibrotic, mesenchymal stem cells (MSCs)-treated fibrotic lives. Strikingly, unearth a ubiquitous two-stage power-law rheology across different time scales with exponents distribution profiles highly correlated to status. Moreover, our self-similar hierarchical theory effectively captures delicate changes dynamical livers. Notably, viscoelastic multiscale indexes (i.e., elastic stiffnesses hierarchies) characteristics prominently vary fibrosis MSCs therapy. This study unveils underscores potential proposed criteria evolution

Language: Английский

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Cortical polarity ensures its own asymmetric inheritance in the stomatal lineage to pattern the leaf surface

Science, Journal Year: 2023, Volume and Issue: 381(6653), P. 54 - 59

Published: July 6, 2023

Asymmetric cell divisions specify differential fates across kingdoms. In metazoans, preferential inheritance of fate determinants into one daughter frequently depends on polarity-cytoskeleton interactions. Despite the prevalence asymmetric throughout plant development, evidence for analogous mechanisms that segregate remains elusive. Here, we describe a mechanism in Arabidopsis leaf epidermis ensures unequal fate-enforcing polarity domain. By defining cortical region depleted stable microtubules, domain limits possible division orientations. Accordingly, uncoupling from microtubule organization during mitosis leads to aberrant planes and accompanying identity defects. Our data highlight how common biological module, coupling segregation through cytoskeleton, can be reconfigured accommodate unique features development.

Language: Английский

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