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Pochitaloff, M.

Publications and source records attributed to Pochitaloff, M..

3 recordsLinked to original sources

Stress-driven tissue fluidization physically segments vertebrate somites

The precise and robust formation of embryonic structures is essential for the function of the organism. During somitogenesis, genetic traveling waves in the presomitic mesoderm orchestrate somite formation and the segmentation of the vertebrate body axis. While key molecular and genetic aspects of this process are known, the mechanical events required to robustly define sharp somite boundaries and physically segment the presomitic mesoderm remain unclear. Here we show that both mechanical noise in the tissue and somite boundary tension are optimized to define sharp somite boundaries and robustly segment the body axis. We find that a large, actomyosin-driven increase in boundary tension progressively straightens the nascent somite-somite boundary. While noise is typically believed to be detrimental to robustness, our results show how mechanical noise in the tissue, introduced by active tension fluctuations at cell contacts, is necessary to fully straighten somite boundaries and minimize variation across individuals. Chemical and optogenetic perturbations of both boundary tension and mechanical noise in the surrounding tissue show that zebrafish embryos optimally tune these quantities to the values necessary to ensure maximal somite boundary straightness. Altogether, these results reveal the physical mechanism of somite formation in zebrafish and uncover how optimal mechanical noise helps robustly shape embryonic structures.

biophysics

Mechanics of the cellular microenvironment as perceived by cells in vivo

Tissue morphogenesis and repair, as well as organ homeostasis, require cells to constantly monitor their 3D microenvironment and adapt their behaviors in response to local biochemical and mechanical cues1-6. In vitro studies have shown that substrate stiffness and stress relaxation are important mechanical parameters in the control of cell proliferation and differentiation, stem cell maintenance, cell migration 7-11, as well as tumor progression and metastasis12,13. Yet, the mechanical parameters of the microenvironment that cells perceive in vivo, within 3D tissues, remain unknown. In complex materials with strain- and time-dependent material properties, the perceived mechanical parameters depend both on the strain and timescales at which the material is mechanically probed14. Here, we quantify in vivo and in situ the mechanics of the cellular microenvironment that cells probe during vertebrate presomitic mesoderm (PSM) specification. By analyzing the magnitude and dynamics of endogenous, cell-generated strains, we show that individual cells preferentially probe the stiffness associated with deformations of the supracellular, foam-like tissue architecture. We reveal how stress relaxation leads to a perceived microenvironment stiffness that decreases over time, with cells probing the softest regime. While stress relaxation timescales are spatially uniform in the tissue, most mechanical parameters, including those probed by cells, vary along the anteroposterior axis, as mesodermal progenitors commit to different lineages. Understanding the mechanical parameters that cells probe in their native 3D environment is important for quantitative studies of mechanosensation in vivo2-4,6,15 and can help design scaffolds for tissue engineering applications16-18.

biophysics

Embryonic Tissues as Active Foams

The physical state of embryonic tissues emerges from non-equilibrium, collective interactions among constituent cells. Cellular jamming, rigidity transitions and characteristics of glassy dynamics have all been observed in multicellular systems, but there is no unifying framework to describe all these behaviors. Here we develop a general computational framework that enables the description of embryonic tissue dynamics, accounting for the presence of extracellular spaces, complex cell shapes and tension fluctuations. In addition to previously reported rigidity transitions, we find a distinct rigidity transition governed by the magnitude of tension fluctuations. Our results indicate that tissues are maximally rigid at the structural transition between confluent and non-confluent states, with actively-generated tension fluctuations controlling stress relaxation and tissue fluidization. Comparing simulation results to experimental data, we show that tension fluctuations do control rigidity transitions in embryonic tissues, highlighting a key role of non-equilibrium tension dynamics in developmental processes.

biophysics