Embryonic Tissues as Active Foams

Abstract

1The 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.Many essential processes in multicellular organisms, from organ formation to tissue homeostasis, require a tight control of the tissue physical state 1, 2 . While tissue mechanics and structure at supracellular scales emerge from the collective physical interactions among the constituent cells, their control occurs at cell and subcellular levels. Bridging these scales is essential to understand the physical nature of active (non-equilibrium) multicellular systems and to identify the processes that cells use to control the physical state of embryonic tissues.In vitro experiments of cell monolayers on substrates have revealed characteristics of glassy 2 dynamics 3, 4 and rigidity transitions 5-7 , which are thought to be linked to biological function and multiple pathologies. In contrast, suspended epithelial monolayers are largely solid-like in vitro 8 and show evidence of fracture in vivo 9 . Experiments in embryonic tissues have shown characteristics of glassy dynamics in cell movements 10 , viscous behavior at long-timescales 11 and also structural signatures reminiscent of jamming transitions 12 . Recent in vivo experiments in developing zebrafish embryos showed the existence of a rigidity (fluid-to-solid) transition underlying the formation of the vertebrate body axis, revealing a functional role of rigidity transitions in embryonic development 13 . It is, however, unclear how cells control rigidity transitions in multicellular systems and, more generally, whether all these observed phenomena share a common physical origin.The physical behavior of multicellular systems has been studied theoretically using various approaches. Vertex models [14][15][16][17][18][19] and Cellular Potts models 20, 21 , which account for cell geometry and use equilibrium formulations to describe the physical state of the system, predict a densityindependent rigidity transition in confluent systems that is solely controlled by cell...

Stress-driven tissue fluidization physically segments vertebrate somites

“…These observations reveal spatiotemporal changes in the somite physical state over the course of somitogenesis, with the fluidization of the tissue adjacent to the posterior boundary occurring as the tissue surrounding the anterior boundary rigidifies. Together with previous measurements of stress relaxation in the paraxial mesoderm 30,40 , our results indicate that at the timescales of somite formation (30 minutes) both the interior of the somite and its anterior boundary are in a solid state (albeit with a more rigid anterior boundary), while the posterior boundary is transiently fluidized during the physical segmentation of the PSM.…”

Using optogenetics to link myosin patterns to contractile cell behaviors during convergent extension

“…Active fluctuations in tension and shape can help to overcome these energy barriers and promote the ability of a tissue to remodel and flow-tissue fluidity. Indeed, recent experimental studies point toward exactly such a role for active fluctuations in promoting fluidity within tissues (40,41). Future studies of the biophysics of cell rearrangements in the germband will be needed to explore further how active fluctuations might contribute to oriented cell rearrangements in both wild-type and mutant embryos.…”

“…Fluctuations or pulses in myosin accumulation and associated changes in apical cell shape have been described in many epithelia and are thought to play key roles in diverse cellular processes during morphogenesis, including apical cell constriction and cell intercalation (1,67). Moreover, active fluctuations in cell shape and actomyosin accumulation have been proposed to play key roles in promoting cell rearrangement and tissue fluidity in some contexts (40,41). While cell area fluctuations have been reported in the germband during axis elongation (34,37,66), their role in the process remains unclear.…”

“…In addition to junctional actomyosin, a dynamic actomyosin meshwork in the medial-apical domain of germband cells exhibits polarized flows and pulsatile behaviors that are thought to contribute to pulsatile fluctuations in cell junctions and apical cell areas and to cell intercalation (34)(35)(36)(37)(38)(39). Recent theoretical and experimental studies point toward important roles both for active fluctuations in cell shape and junctions (40,41) and for details of cellular packings within tissues (42)(43)(44)(45) in the physics of cell rearrangements and the ability of a tissue to remodel and flow, i.e. tissue fluidity.…”

Cell cycle-dependent active stress drives epithelia remodeling

“…collective solidification) caused by changes in density or cell mechanics, or instead by a decrease in active stress fluctuations in a material that remains fluid-like. Particle-based models for tissues predict decreased cell motion arising from reduced interstitial space at increased cell density (12, 22, 23, 35). In contrast, vertex models predict that the cell density is not a direct control parameter for cell dynamics (24).…”