Search

Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregate's shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses (“fluctuation-induced flow”). If not, changing the aggregate's shape requires a sufficiently large applied stress (“stress-induced flow”). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress τ*, the aggregate as a whole flows with an apparent viscosity η*, and at higher stress it is a shear-thinning fluid. An increasing cell–cell tension results in a higher η* (and thus a slower stress relaxation time t c ). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find t c of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration.

Apparent tissue surface tension allows the quantification of cell-cell cohesion and was reported to be a powerful indicator for the cellular rearrangements that take place during embryonic development or for cancer progression. The measurement is realized with a parallel compression plate tensiometer using the capillary laws. Although it was introduced more than a decade ago, it is based on various geometrical or physical approximations. Surprisingly, these approximations have never been tested. Using a novel tensiometer, we compare the two currently used methods to measure tissue surface tension and propose a third one, based on a local polynomial fit (LPF) of the profile of compressed droplets or cell aggregates. We show the importance of measuring the contact angle between the plate and the drop/aggregate to obtain real accurate measurement of surface tension when applying existing methods. We can suspect that many reported values of surface tension are greatly affected because of not handling this parameter properly. We show then the benefit of using the newly introduced LPF method, which is not dependent on this parameter. These findings are confirmed by generating numerically compressed droplet profiles and testing the robustness and the sensitivity to errors of the different methods., Comment: 14 pages, 3 figures

International audience; What governs tissue organization and movement? If molecular and genetic approaches are able to give some answers on these issues, more and more works are now giving a real importance to mechanics as a key component eventually triggering further signaling events. We chose embryonic cell aggregates as model systems for tissue organization and movement in order to investigate the origin of some mechanical constraints arising from cells organization. Steinberg et al. proposed a long time ago an analogy between liquids and tissues and showed that indeed tissues possess a measurable tissue surface tension and viscosity. We question here the molecular origin of these parameters and give a quantitative measurement of adhesion versus contractility in the framework of the differential interfacial tension hypothesis. Accompanying surface tension measurements by angle measurements (at vertexes of cell-cell contacts) at the cell/medium interface, we are able to extract the full parameters of this model: cortical tensions and adhesion energy. We show that a tunable surface tension and viscosity can be achieved easily through the control of cell-cell contractility compared to cell-medium one. Moreover we show that -catenin is crucial for this regulation to occur: these molecules appear as a catalyser for the remodeling of the actin cytoskeleton underneath cell-cell contact, enabling a differential contractility between the cell-medium and cell-cell interface to take place.