Analogies with inert soft condensed matter--such as viscoelastic liquids, pastes, foams, emulsions, colloids, and polymers--can be used to investigate the mechanical response of soft biological tissues to forces. A variety of experimental techniques and biophysical models have exploited these analogies allowing the quantitative characterization of the mechanical properties of model tissues, such as surface tension, elasticity, and viscosity. The framework of soft matter has been successful in explaining a number of dynamical tissue behaviors observed in physiology and development, such as cell sorting, tissue spreading, or the escape of individual cells from a tumor. However, living tissues also exhibit active responses, such as rigidity sensing or cell pulsation, that are absent in inert soft materials. The soft matter models reviewed here have provided valuable insight in understanding morphogenesis and cancer invasion and have set bases for using tissue engineering within medicine.

We study the spreading of spheroidal aggregates of cells, expressing a tunable level of E-cadherin molecules, on glass substrates decorated with mixed fibronectin and polyethylene glycol. We observe the contact area by optical interferometry and the profile by side-view microscopy. We find a universal law of aggregate spreading at short times, which we interpret through an analogy with the spreading of viscoelastic droplets. At long times, we observe either partial wetting or complete wetting, with a precursor film of cells spreading around the aggregate with two possible states. In strongly cohesive aggregates this film is a cellular monolayer in the liquid state, whereas in weakly cohesive aggregates, cells escape from the aggregate, forming a 2D gas. The escape of isolated cells is a physical mechanism that appears also to be present in the progression of a noninvasive tumor into a metastatic malignant carcinoma, known as the epithelial-mesenchymal transition.collective migration | cell adhesion | tissue viscoelasticity | tumor invasion T issue spreading is a fundamental process in embryonic development (1-3), wound healing (4), and cancer invasion and propagation. A tumor is not malignant if it remains cohesive. Understanding how noninvasive tumor cells become metastatic is the most prominent challenge in current cancer research. The first step of cancer propagation (invasion) is characterized by a loss of cell adhesion associated to an increase in cell motility, followed by an entry into blood circulation (intravasation), an escape into a new tissue (extravasation), and the proliferation leading to a secondary tumor (5). The loss of cell adhesion, characteristic of aggressive metastatic cancer, is analogous to that of the epithelial-mesenchymal transition (EMT) during embryonic development (6, 7), which is a key process during gastrulation (8) or neural crest development (9). A repression of E-cadherin expression (involved in the formation of adherens junctions between cells mediated by homophilic ligation in the presence of calcium) has been reported for cells undergoing an EMT transition (10). Here we study the role of E-cadherin expression in the wetting behavior of tissues. We use as a model system cellular aggregates of variable cohesivity, spreading on glass substrates of variable adhesivity.Spherical cellular aggregates are useful in vitro systems to study the properties of tissues. The characterization of tissue mechanics through viscosity has been debated since the pioneering work of Steinberg. He demonstrated that embryonic tissues behave like liquids and are characterized by a well-defined surface tension (11). Mixing cells of two tissues, he observed cell sorting: The tissue with the lower surface tension surrounds the tissue with a higher tension (12-14). If two aggregates are brought in contact, they coalesce to form a single, larger spheroid. The fusion of two aggregates (15, 16) leads to the determination of the capillary velocity V Ã ¼ γ∕η, where γ is the surface tension and η is the viscos...

The inhibition of tissue spreading is of great interest for medical applications, including the prevention of tumor mass dispersal to avoid cancer propagation. While chemical approaches have previously been reported to control tissue spreading, here we investigate a physical mechanism to inhibit spreading. We study the effect of substrate rigidity on the statics and dynamics of spreading of spheroidal aggregates of cells deposited on fibronectin-coated polydimethylsiloxane (PDMS) and polyacrylamide (PAA) substrates by tuning the elastic modulus E from 0.2 kPa to 1.8 MPa while maintaining a constant chemical environment. On rigid substrates, above a threshold elastic modulus E c z 8 kPa, the aggregate spreads with a cellular monolayer expanding around the aggregate (''complete wetting''). The kinetics of spreading obeys a diffusive law with a diffusion coefficient D(E) presenting a maximum that we interpret theoretically. At E ¼ E c , we observe a wetting transition, and on soft substrates (E < E c ), the aggregate no longer spreads. Instead, it flattens and adopts an equilibrium shape of a spherical cap with a finite contact angle (''partial wetting''). These results provide insight into the relevant physical principles underlying cellular aggregate spreading, a phenomenon of interest in the understanding of tumor spreading and invasion.