Embryonic tissues as active foams

Abstract

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.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 .

Viscoelastic Networks: Forming Cells and Tissues

“…In contrast, changes in cell rearrangements, cell-cell adhesion, contractility and cell division rates were shown to trigger changes in the tissue scale material properties (Figure 1D) [11-13, 86-88, 93]. This agrees with extensive theoretical work inferring tissue material phase transitions based on certain cell parameters such as cell motility and adhesion [27,28,32,41], and quantitatively linking tissue rigidity to cell-cell connectivity and adhesion [29], but not directly to the rigidity of individual cells.…”

“…Since, in a tilling of cells, deformation can only arise through cell-cell rearrangements, vertex models mostly focus the analysis on the study of the energy penalties associated with these cell-cell rearrangements. Such rearrangements can for example be induced by differences in cell-cell adhesion and cortical tension or active tension fluctuations [27,28,32,125]. It is implicitly postulated that the results at that level of abstraction will project into the material properties of the system.…”

“…Importantly, these properties may imply an interesting departure from the framework proposed by inanimate material science, and proposes a theoretical framework that extends to biological materials. In principle, vertex models have been postulated to model confluent tissues, with recent approaches extending the framework to non-confluent tissues [32]. The essential problem vertex models try to answer is: what are the energetic costs for cell migration within a tissue?…”

“…In spite of the numerical evidence that the emergence in the linear regime of the shear modulus coincides with the emergence of theoretical energy barriers in disordered systems, it is currently still unclear what is the theoretical background that could explain the emergence of viscoelastic properties from the theoretical framework of vertex models. Finally, an extension of this vertex model has been developed for non-confluent tissues where stochastic fluctuations in cell surface tensions, density and cell rearrangements control rigidto-fluid transitions [32]. This contribution detaches the framework of vertex models from the structural constraints that confluency imposes, hence broadening their application in biological tissues.…”

“…Last, similar to the viscoelasticity of non-living materials, viscoelasticity of cells and tissues is a property arising from their underlying structure, defined by the way macromolecules and cells interact [1,8,15,[25][26][27][28][29]. Several theoretical frameworks have for long been used in non-living materials to link the microscopic structure to the macroscopic viscoelastic properties (Supplementary Box S1), showing that viscoelasticity may behave as an emergent property [27][28][29][30][31][32], in the same way, e.g., temperature arises non-trivially from microscopic particle motion in statistical mechanics [14]. How macroscopic viscoelasticity can be predicted by the interactions of the microscopic constituents of living cells and tissues is an open question at the interface of statistical and soft matter physics with molecular and cell biology, and the main topic of this review.…”