Cell aggregation in monolayer culture: clues to a universal kinetics

Cell aggregation is a dynamic and complex process ubiquitous in life. It occurs in morphogenesis, from organisms situated at the border between single and multicellular life forms, for instance \textit{Dyctyostelium discoideum} , to mammals in which tissues are formed by the assembly of migratory and similar cells into cohesive groups. Also, aggregation disorders are present in numerous diseases. The aggregation of animal cells in culture comprises a series of motility, collision and adhesion processes of basic relevance for tissue engineering, bioseparations, oncology research and \textit{in vitro} drug testing. In the present work, we characterize the aggregation kinetics of normal and cancer cells in culture by determining their cluster size distribution functions. Our experiments reveal that the complementary cumulative distributions for eight cell lines from epithelial and mesenchymal origins are described by stretched exponential functions. Also, we find that as time evolves and the cell density increases, a dynamical phase transition occurs from an aggregation regime described by monotonically decreasing cluster size distributions to another one in which these distributions are nonmonotonic, exhibiting local maxima at large cluster sizes. Subtly, the universality of the stretched exponential distributions admits distinct cluster growth processes controlled by motility and adhesion traits of the cells. Finally, both analytical calculations based on a Smoluchowski-like mean-field approach and simulations of an agent based model of the cell aggregation process were developed in order to describe the experimentally obtained cluster size distributions functions.

This work was partially supported by FAPEMIG.