Biology subjects

Minc, N.

Publications and source records attributed to Minc, N..

7 recordsLinked to original sources

bioRxiv2025

Mechanical coordination between anaphase A and B drives asymmetric chromosome segregation

Chromosome segregation during anaphase occurs through two mechanistically distinct processes: anaphase A, in which chromosomes move toward spindle poles, and anaphase B, in which the anaphase spindle elongates through cortical astral microtubule pulling forces. Caenorhabditis elegans embryos have been thought to rely primarily on anaphase B, with little to no contribution from anaphase A. Here, we uncover a novel anaphase A mechanism in C. elegans embryos, driven by the kinesin-13 KLP-7MCAK and opposed by the kinesin-12 KLP-18. We found that the extent of chromosome segregation during anaphase A is asymmetrically regulated by cell polarity cues and modulated by mechanical tension within the spindle, generated by opposing forces acting on chromosomes and spindle poles. Additionally, we found that the contribution of anaphase A to chromosome segregation increases progressively across early embryonic divisions. These findings uncover an unexpected role for anaphase A in early C. elegans development and reveal a KLP-7MCAK-dependent mechanical coordination between anaphase A and anaphase B driven chromosome segregation. eTOC summaryDias Maia Henriques et al. uncover an anaphase A pathway, driven by the kinesin-13 KLP-7 and opposed by the kinesin-12 KLP-18, that contributes to chromosome segregation in early C. elegans embryos. Its activity is regulated by spindle tension, cell polarity cues, and progressively increases during early embryonic divisions.

cell biology↗

bioRxiv2024

Mechanical Strategies Supporting Growth and Size Diversity in Filamentous Fungi

The stereotypical tip growth of filamentous fungi supports their lifestyles and functions. It relies on the polarized remodeling and expansion of a protective elastic cell wall (CW) driven by large cytoplasmic turgor pressure. Remarkably, hyphal filament diameters, and cell elongation rates can vary extensively among different fungi. To date, however, how fungal cell mechanics may be adapted to support these morphological diversities while ensuring surface integrity remains unknown. Here, we combined super-resolution imaging and deflation assays, to measure local CW thickness, elasticity and turgor in a set of fungal species spread on the evolutionary tree that span a large range in cell size and growth speeds. While CW elasticity exhibited dispersed values presumably reflecting differences in CW composition, both thickness and turgor scaled in dose-dependence with cell diameter and growth speeds. Notably, larger cells exhibited thinner lateral CWs, and faster cells thinner apical CWs. Counterintuitively, turgor pressure was also inversely scaled with cell diameter and tip growth speed, challenging the idea that turgor is the primary factor dictating tip elongation rates. We propose that fast growing cells with rapid CW turnover have evolved strategies based on a less turgid cytoplasm and thin walls to safeguard wall integrity and survival.

cell biology↗

bioRxiv2022

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

Many studies of cytoplasm rheology have focused on small components in the sub-micrometer scale. However, the cytoplasm also baths large organelles like nuclei, microtubule asters or spindles that often take significant portions of cells and move across the cytoplasm to regulate cell division or polarization. Here, we translated passive components of sizes ranging from few up to ~50 percent of the cell diameter, through the vast cytoplasm of live sea urchin eggs, with calibrated magnetic forces. Creep and relaxation responses indicate that for objects larger than the micron size, the cytoplasm behaves as a Jeffreys material, viscoelastic at short time-scales and fluidizing at longer times. However, as components size approached that of cells, cytoplasm viscoelastic resistance increased in a non-monotonic manner. Flow analysis and simulations suggest that this size-dependent viscoelasticity emerges from hydrodynamic interactions between the moving object and the static cell surface. This effect also yields to position-dependent viscoelasticity with objects initially closer to the cell surface being harder to displace. These findings suggest that the cytoplasm hydrodynamically couples large organelles to the cell surface to restrain their motion, with important implications for cell shape sensing and cellular organization. Significance StatementLarge-sized organelles like nuclei or mitotic spindles typically translocate through the cytoplasm to regulate cell division or polarity, but their frictional interaction with the cytoplasm and the cell surface remain poorly addressed. We used in vivo magnetic tweezers, to move passive components in a range of size in the cytoplasm of living cells. We found that the mobility of objects with sizes approaching that of cells, can be largely reduced as a result of hydrodynamic interactions that couple objects and the cell surface through the cytoplasm fluid.

biophysics↗

bioRxiv2020

IN VITRO RECONSTITUTION OF DYNEIN FORCE EXERTION IN BULK CYTOPLASM

The forces generated by Microtubules (MTs) and their associated motors orchestrate essential cellular processes ranging from vesicular trafficking to centrosome positioning [1, 2]. To date, most studies have focused on force exertion from motors anchored on a static surface, such as the cell cortex in vivo or glass surfaces in vitro [2-4]. However, motors also transport large cargos and endomembrane networks, whose hydrodynamic interactions with the viscous cytoplasm should generate sizable forces in bulk. Such forces may contribute to MT aster centration, organization and orientation [5-14], but have yet to be evidenced and studied in a minimal reconstituted system. By developing a bulk motility assay, based on stabilized MTs and dynein-coated beads freely floating in a viscous medium away from any surface, we demonstrate that the motion of a cargo exerts a pulling force on the MT and propels it in opposite direction. Quantification of resulting MT movements for different motors, motor velocities, over a range of cargo size and medium viscosities, shows that the efficiency of this mechanism is primarily determined by cargo size and MT length. Forces exerted by cargos are additive, allowing us to recapitulate tug-of-war situations, or bi-dimensional motions of minimal asters. These data also reveal unappreciated effects of the nature of viscous crowders and hydrodynamic interactions between cargos and MTs, likely relevant to understand this mode of force exertion in living cells. This study places endomembrane transport as a significant mode of MT force exertion with far-reaching consequences for cellular organization.

biophysics↗

bioRxiv2019

The perinuclear ER scales nuclear size independently of cell size in early embryos

SUMMARYNuclear size plays pivotal roles in gene expression, embryo development, and disease. A central hypothesis in organisms ranging from yeast to vertebrates is that nuclear size scales to cell size. This implies that nuclei may reach steady state sizes set by limiting cytoplasmic pools of size-regulating components. By monitoring nuclear dynamics in early sea urchin embryos, we found that nuclei undergo substantial growth in each interphase, reaching a maximal size prior to mitosis that declined steadily over the course of development. Manipulations of cytoplasmic volume through multiple chemical and physical means ruled out cell size as a major determinant of nuclear size and growth. Rather, our data suggest that the perinuclear endoplasmic reticulum, accumulated through dynein activity, serves as a limiting membrane pool that sets nuclear surface growth rate. Partitioning of this local pool at each cell division modulates nuclear growth kinetics and dictates size scaling throughout early development.

cell biology↗

bioRxiv2018

SYSTEMATIC MAPPING OF CELL WALL MECHANICS IN THE REGULATION OF CELL MORPHOGENESIS

Walled cells of plants, fungi and bacteria, come with a large range of shapes and sizes, which are ultimately dictated by the mechanics of their cell wall. This stiff and thin polymeric layer encases the plasma membrane and protects the cells mechanically by opposing large turgor pressure derived stresses. To date, however, we still lack a quantitative understanding for how local and/or global mechanical properties of the wall support cell morphogenesis. Here, we combine super-resolution imaging, and laser-mediated wall relaxation, to quantitate subcellular values of wall thickness (h) and bulk elastic moduli (Y) in large populations of live mutant cells and conditions affecting cell diameter in the rod-shaped model fission yeast. We find that lateral wall stiffness, defined by the surface modulus, {sigma}=hY, robustly scales with cell diameters. This scaling is valid in tens of mutants covering various functions, within the population of individual isogenic strains, along single misshaped cells, and even across the fission yeasts clade. Dynamic modulations of cell diameter by chemical and/or mechanical means suggest that the cell wall can rapidly adapt its surface mechanics, rendering stretched wall portions stiffer than unstretched ones. Size-dependent wall stiffening constrains diameter definition and limits size variations, and may also provide and efficient mean to keep elastic strains in the wall below failure strains potentially promoting cell survival. This quantitative set of data impacts our current understanding of the mechanics of cell walls, and its contribution to morphogenesis.

biophysics↗

bioRxiv2018

MECHANOSENSATION DYNAMICALLY COORDINATES POLAR GROWTH AND CELL WALL ASSEMBLY TO PROMOTE CELL SURVIVAL

How growing cells cope with size expansion while ensuring mechanical integrity is not known. In walled cells, such as those of microbes and plants, growth and viability are both supported by a thin and rigid encasing cell wall (CW). We deciphered the dynamic mechanisms controlling wall surface assembly during cell growth, using a novel sub-resolution microscopy approach to monitor CW thickness in live rod-shaped fission yeast cells. We found that polar cell growth yielded wall thinning, and that thickness negatively influenced growth. Thickness at growing tips exhibited oscillating behavior with thickening phases followed by thinning phases, indicative of a delayed feedback promoting thickness homeostasis. This feedback was mediated by mechanosensing through the cell wall integrity pathway, which probes strain in the wall to adjust synthase localization and activity to surface growth. Mutants defective in thickness homeostasis lysed by rupturing the wall demonstrating its essential role for walled cell survival.

cell biology↗