Biology subjects

Moeendarbary, E.

Publications and source records attributed to Moeendarbary, E..

4 recordsLinked to original sources

bioRxiv2024

The cytoplasm of living cells can sustain transient and steady intracellular pressure gradients

Understanding the physical basis of cellular shape change in response to both internal and external mechanical stresses requires characterisation of cytoplasmic rheology. At subsecond time-scales and micron length-scales, cells behave as fluid-filled sponges in which shape changes necessitate intracellular fluid redistribution. However, whether these cytoplasmic poroelastic properties play an important role in cellular mechanical response over length- scales and time-scales relevant to cell physiology remains unclear. Here, we investigated whether and how a localised deformation of the cell surface gives rise to transient intracellular flows spanning several microns and lasting seconds. Next, we showed that pressure gradients induced in the cytoplasm can be sustained over several minutes. We found that stable pressure gradients can arise from the combination of cortical tension, cytoplasmic poroelasticity and water flows across the membrane. Overall our data indicate that intracellular cytosolic flows and pressure gradients may play a much greater role than currently appreciated, acting over time- and length-scales relevant to mechanotransduction and cell migration, signifying that poroelastic properties need to be accounted for in models of the cell. Significance statementUnderstanding how cells change shape dynamically under the influence of external and internal forces requires characterisation of the mechanical response of the cytoplasm, the viscous material that fills their interior. The cytoplasm consists of a porous solid phase bathed in a fluid, the cytosol. As the cytoplasm is incompressible, any cellular shape change necessitates redistribution of the cytosol within the cell and its flow rate sets the time-scale for deformation. How the cytoplasmic mechanical response affects cell physiology remains poorly understood. We show that the unique physical properties of the cytoplasm allow cells to sustain cellular-scale pressure gradients over minute time-scales. As a consequence, pressure-driven mechanisms may play a much greater role in cell physiology than currently appreciated.

biophysics↗

bioRxiv2021

Modeling the three-way feedback between cellular contractility, actin polymerization, and adhesion turnover resolves the contradictory effects of RhoA and Rac1 on endothelial junction dynamics

The formation and recovery of gaps in the vascular endothelium governs a wide range of physiological and pathological phenomena, from angiogenesis to atherosclerosis and tumor cell extravasation. However, the interplay between the mechanical and signaling processes that drive dynamic behavior in vascular endothelial cells is not well understood. In this study, we propose a chemo-mechanical model to investigate the maintenance of endothelial junctions as dependent on the crosstalk between actomyosin contractility, VE-cadherin bond turnover, and actin polymerization, which mediate the forces exerted on the cell-cell interface. Our theoretical model reveals that active cell tension can stabilize cadherin bonds within an adhesion, but excessive RhoA signaling can drive bond dissociation and junction failure. While Rac1-mediated actin polymerization aids gap closure, high levels of Rac1 may also facilitate junction weakening. Combining the modeling framework with novel experiments, we identify how dynamic rupture and heal cycles emerge and, further, describe why gaps tend to localize at multi-cell contacts. Beyond, our analysis also indicates that a critical balance between RhoA and Rac1 expression is required to maintain junction stability and limit endothelial dysfunction. The model predicts how pharmacological modulation of actin polymerization and cell contractility impacts junction stability, with predictions subsequently validated experimentally. Our proposed framework can help guide the development of therapeutics that target the Rho family of GTPases and downstream active mechanical processes.

biophysics↗

bioRxiv2018

Balance of Mechanical Forces Drives Endothelial Gap Formation and May Facilitate Cancer and Immune-Cell Extravasation

The formation of gaps in the endothelium is a crucial process underlying both cancer and immune cell extravasation, contributing to the functioning of the immune system during infection, the unfavorable development of chronic inflammation and tumor metastasis. Here, we present a stochastic-mechanical multiscale model of an endothelial cell monolayer and show that the dynamic nature of the endothelium leads to spontaneous gap formation, even without intervention from the transmigrating cells. These gaps preferentially appear at the vertices between three endothelial cells, as opposed to the border between two cells. We quantify the frequency and lifetime of these gaps, and validate our predictions experimentally. Interestingly, we find experimentally that cancer cells also preferentially extravasate at vertices, even when they first arrest on borders. This suggests that extravasating cells, rather than initially signaling to the endothelium, might exploit the autonomously forming gaps in the endothelium to initiate transmigration.

bioengineering↗

bioRxiv2018

Predicting local tissue mechanics using immunohistochemistry

Local tissue stiffness provides an important signal to which cells respond in vivo. However, assessing tissue mechanics is currently challenging and requires sophisticated technology. We here developed a model quantitatively predicting nervous tissue stiffness heterogeneities at cellular resolution based on cell density, myelin and GFAP fluorescence intensities. These histological parameters were identified by a correlation analysis of atomic force microscopy-based elasticity maps of spinal cord sections and immunohistochemical stainings. Our model provides a simple tool to estimate local stiffness distributions in nervous tissue, and it can easily be expanded to other tissue types, thus paving the way for studies of the role of mechanical signals in development and pathology.

biophysics↗