Mechanosensitivity and Motility of Cellular Aggregates

Abstract

We describe the biomechanics of multicellular aggregates, a model system for tissues and tumors. We first characterize the tissue mechanical properties (surface tension, elasticity, viscosity) by a new pipette aspiration technique. The aggregate exhibits a viscoelastic response but, unlike an inert fluid, we observe aggregate reinforcement with pressure, which for a narrow range of pressures results in pulsed contractions or “shivering”. We interpret this reinforcement as a mechanosensitive active response of the acto-myosin cortex. Such an active behavior has previously been found to cause tissue pulsation during dorsal closure of Drosophila embryo.We then describe aggregate spreading on decorated glass substrates. We find a universal spreading law at short time, analogous to that of a viscoelastic drop. At long time, we observe a precursor film spreading around the aggregate. Depending on aggregate cohesion, this precursor film can be a dense cellular monolayer (“liquid state”) or consist of individual cells escaping from the aggregate body (“gas state”). The transition from “liquid” to “gas state” appears also to be present in the progression of a tumor from noninvasive to metastatic, known as the epithelial-mesenchymal transition.Finally, we describe the effect of the substrate rigidity on the spreading of aggregates. We observe that aggregates spreading on rigid gels, do not spread on soft gels: we can induce a wetting transition from complete to partial wetting by decreasing the elastic modulus of the substrate. Moreover, near this transition, we observe a spontaneous motion of the aggregates, where all cells have a cooperative motion forming a giant keratocytes.