Coaction of intercellular adhesion and cortical tension specifies tissue surface tension

Abstract

In the course of animal morphogenesis, large-scale cell movements occur, which involve the rearrangement, mutual spreading, and compartmentalization of cell populations in specific configurations. Morphogenetic cell rearrangements such as cell sorting and mutual tissue spreading have been compared with the behaviors of immiscible liquids, which they closely resemble. Based on this similarity, it has been proposed that tissues behave as liquids and possess a characteristic surface tension, which arises as a collective, macroscopic property of groups of mobile, cohering cells. But how are tissue surface tensions generated? Different theories have been proposed to explain how mesoscopic cell properties such as cell-cell adhesion and contractility of cell interfaces may underlie tissue surface tensions. Although recent work suggests that both may be contributors, an explicit model for the dependence of tissue surface tension on these mesoscopic parameters has been missing. Here we show explicitly that the ratio of adhesion to cortical tension determines tissue surface tension. Our minimal model successfully explains the available experimental data and makes predictions, based on the feedback between mechanical energy and geometry, about the shapes of aggregate surface cells, which we verify experimentally. This model indicates that there is a crossover from adhesion dominated to cortical-tension dominated behavior as a function of the ratio between these two quantities.differential adhesion hypothesis | differential interfacial tension hypothesis | mathematical modeling | cell aggregate geometry | self-assembly I t is well established that many tissues behave like liquids on long timescales. Cell tracking in vivo and in vitro highlights (i) largescale flows, (ii) exchange of nearest neighbors in a cellular aggregate, and (iii) rounding-up and fusion of aggregates (1). Macroscopic rheological properties such as surface tension can be measured using a tissue surface tensiometer (TST) (1-8) or micropipette aspiration (9), and surface tension can be used to explain tissue self-organization in embryogenesis (8, 10-12) or cancer (13,14). In particular, cell sorting and tissue spreading can be explained in terms of tissue surface tensions that differ among cell types (1, 3-5, 8, 15, 16).A full understanding of tissue surface tension as a driving force for biological processes is important, and knowledge of its cellular origins would allow us to intelligently design drugs and treatments to alter tissue organization. Two opposing theories about the mesoscopic origin of tissue surface tension have coexisted over the last 30 years. One, the differential adhesion hypothesis (DAH), postulates that in analogy to ordinary fluids, tissue surface tension is proportional to the intensity of the adhesive energy between the constituent cells, which are treated as point objects. The DAH has proven successful in a variety of studies with cell lines (2-5, 15) , malignant (13, 14) and embryonic tissues (1,5,8,16) and is widely accepted (12...

Glassy dynamics in three-dimensional embryonic tissues

“…We believe our model fails to correctly capture the magnitude of tissue surface tension because it likely depends on cell shapes and a strong feedback between adhesion and cortical tension that occurs at tissue interfaces, as discussed in other work [24]. We could augment our model to account for this by replacing the isotropic interaction given by electronic supplementary material, equation S2, by a non-isotropic interaction for surface cells.…”

“…Tissue surface tension is a well-studied property of tissues [ quantifies how much a macroscopic tissue resists changes to its surface area. Tissue surface tension causes zebrafish explants to round-up as shown in figure 5 and governs cell sorting in embryonic tissues [1,24]. The first set of simulations for a quantitative comparison are tissue surface tension parallel plate compression tests, where we seek to replicate the experiment in which a cellular aggregate is compressed between two parallel plates.…”

“…Maternal zygotic one-eyed pinhead (MZoep) and 50-100 pg of cyclops mRNA-injected wild-type zebrafish aggregates, corresponding to ectoderm and mesendoderm, respectively, were generated and fluorescently labelled as previously described [1,24,26].…”

Tissue growth controlled by geometric boundary conditions: a simple model recapitulating aspects of callus formation and bone healing

“…(2) There is a surface stress, which results in a surface curvature-dependent internal pressure inside the tissue [9,11,12,21,41]. (3) Growth of a tissue, by cell proliferation and extracellular matrix formation, depends on its pressure through the growth equation.…”

“…Depending on the physical environment, these boundaries may either be static, as is the case for solid substrates, or they may move as new tissue is formed [8]. One important simplification that can be made to help understand this problem is based on the observation that tissues, or at least cell agglomerates, can behave like viscous fluids with measureable surface tensions when observed for sufficiently long timescales [9][10][11][12]. If one describes tissues as fluids, then the equilibrium shape of their boundaries will be determined on one hand by the wettability of any substrates upon which they are sitting [13] and on the other hand by the Laplace -Young equation giving a link between interfacial curvature and tissue pressure [14].…”