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...

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Amoeboid cell motility is a complicated process requiring the regulated activity and localization of many molecules and resulting in the cyclic repetition of a relatively small repertoire of shape changes. These changes are driven by the traction work produced by the cell, which can be estimated by measuring the forces and displacements exerted by the cells on their substrate during migration. We have developed and applied a novel implementation of Principal Component Analysis to identify and sort out the most important shape changes in terms of traction work produced by chemotaxing Dictyostelium cells. For this purpose, we acquired time-lapse recordings of cell shape and traction forces of Dictyostelium cells migrating on deformable substrates. Using wild-type cells as reference, we investigated the effect of altering myosin II activity by studying myosin II null cells and essential light chain null cells. Our results indicate that the spatio-temporal variation of the traction work produced by Dictyostelium cells can be described with a reduced number of modes. In fact, only four modes are needed to account for 65% of the traction work exerted by all cells lines studied. Furthermore, the first mode alone accounts for more than 40% of the traction work. Spatially, this mode consists of the attachment of the cell predominantly at two areas at front and back, contracting towards the center of the cell. The time evolution of this mode is approximately periodic and coincides with the time evolution of cell length. Each one of the remaining modes accounts for less that 10% of the traction work. Their temporal and spatial organization is less clear, suggesting that the cell performs a traction work cycle composed of a repetitive sequence of steps over which random fluctuations are imposed.