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Campas, O.

Publications and source records attributed to Campas, O..

4 recordsLinked to original sources

Mechanical control of tissue shape and morphogenetic flows during vertebrate body axis elongation

Shaping embryonic tissues into their functional morphologies requires cells to control the physical state of the tissue in space and time. While regional variations in cellular forces or cell proliferation have been typically assumed to be the main physical factors controlling tissue morphogenesis, recent experiments have revealed that spatial variations in the tissue physical (fluid/solid) state play a key role in shaping embryonic tissues. Here we theoretically study how the regional control of fluid and solid tissue states guides morphogenetic flows to shape the extending vertebrate body axis. Our results show that both the existence of a fluid-to-solid tissue transition along the anteroposterior axis and the tissue surface tension determine the shape of the tissue and its ability to elongate unidirectionally, with large tissue tensions preventing unidirectional elongation and promoting blob-like tissue expansions. We predict both the tissue morphogenetic flows and stresses that enable unidirectional axis elongation. Our results show the existence of a sharp transition in the structure of morphogenetic flows, from a flow with no vortices to a flow with two counter-rotating vortices, caused by a transition in the number and location of topological defects in the flow field. Finally, comparing the theoretical predictions to quantitative measurements of both tissue flows and shape during zebrafish body axis elongation, we show that the observed morphogenetic events can be explained by the mere existence of a fluid-to-solid tissue transition along the anteroposterior axis. These results highlight the role of spatiotemporally-controlled fluid-to-solid transitions in the tissue state as a physical mechanism of embryonic morphogenesis.

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

Physical constraints on early blastomere packings

At very early embryonic stages, when embryos are composed of just a few cells, establishing the correct packing arrangements (contacts) between cells is essential for the proper development of the organism. As early as the 4-cell stage, the observed cellular packings in different species are distinct and, in many cases, differ from the equilibrium packings expected for simple adherent and deformable particles. It is unclear what are the specific roles that different physical parameters, such as the forces between blastomeres, their division times, orientation of cell division and embryonic confinement, play in the control of these packing configurations. Here we simulate the non-equilibrium dynamics of cells in early embryos and systematically study how these different parameters affect embryonic packings at the 4-cell stage. In the absence of embryo confinement, we find that cellular packings are not robust, with multiple packing configurations simultaneously possible and very sensitive to parameter changes. Our results indicate that the geometry of the embryo confinement determines the packing configurations at the 4-cell stage, removing degeneracy in the possible packing configurations and overriding division rules in most cases. Overall, these results indicate that physical confinement of the embryo is essential to robustly specify proper cellular arrangements at very early developmental stages. Author summaryAt the initial stages of embryogenesis, the precise arrangement of cells in the embryo is critical to ensure that each cell gets the right chemical and physical signals to guide the formation of the organism. Even when the embryo is made of only four cells, different species feature varying cellular arrangements: cells in mouse embryos arrange as a tetrahedron, in the nematode worm C. elegans cells make a diamond and in sea urchins cells arrange in a square configuration. How do cells in embryos of different species control their arrangements? Using computer simulations, we studied how cell divisions, physical contacts between cells and the confinement of the embryo by an eggshell affect the arrangements of cells when the embryos have only 4 cells. We find that the shape of the confining eggshell plays a key role in controlling the cell arrangements, removing unwanted arrangements and robustly specifying the proper contacts between cells. Our results highlight the important roles of embryonic confinement in establishing the proper cell-cell contacts as the embryo starts to develop.

biophysics

Coordinating cell polarization and morphogenesis through mechanical feedback

Many cellular processes require cell polarization to be maintained as the cell changes shape, grows or moves. Without feedback mechanisms relaying information about cell shape to the polarity molecular machinery, the coordination between cell polarization and morphogenesis, movement or growth would not be possible. Here we theoretically and computationally study the role of a genetically-encoded mechanical feedback (in the Cell Wall Integrity Pathway) as a potential coordination mechanism between cell morphogenesis and polarity during budding yeast mating projection growth. We developed a coarse-grained continuum description of the coupled dynamics of cell polarization and morphogenesis as well as 3D stochastic simulations of the molecular polarization machinery in the evolving cell shape. Both theoretical approaches show that in the absence of mechanical feedback (or in the presence of weak feedback), cell polarity cannot be maintained at the projection tip during growth, with the polarization cap wandering off the projection tip, arresting morphogenesis. In contrast, for mechanical feedback strengths above a threshold, cells can robustly maintain cell polarization at the tip and simultaneously sustain mating projection growth. These results indicate that the mechanical feedback encoded in the Cell Wall Integrity pathway can provide important positional information to the molecular machinery in the cell, thereby enabling the coordination of cell polarization and morphogenesis. Author summaryCell migration, morphogenesis and secretion are among the vast number of cellular processes that require cells to define a preferred spatial direction to perform essential tasks. This is achieved by setting an intracellular molecular gradient that polarizes the cell. While the molecular players involved in cell polarization and some of the mechanisms that cells use to establish such molecular gradients are known, it remains unclear how cells maintain polarization as they dramatically change shape during morphogenesis, migration, etc. Here we identify a potential feedback control mechanism, encoded genetically in cells, that provides the molecular polarization machinery with the necessary information about cell geometry to maintain cell polarization during cell shape changes.

biophysics