On the Role of Physics in the Growth and Pattern Formation of Multi-Cellular Systems: What can we Learn from Individual-Cell Based Models?

Abstract

We demonstrate that many collective phenomena in multi-cellular systems can be explained by models in which cells, despite their complexity, are represented as simple particles which are parameterized mainly by their physical properties. We mainly focus on two examples that nevertheless span a wide range of biological sub-disciplines: Unstructured cell populations growing in cell culture and growing cell layers in early animal development. While cultured unstructured cell populations would apriori been classified as particularly suited for a biophysical approach since the degree to which they are committed to a genetic program is expected to be modest, early animal development would be expected to mark the other extreme—here the degree of determinism according to a genetic program would be expected to be very high. We consider a number of phenomena such as the growth kinetics and spatial structure formation of monolayers and multicellular spheroids, the effect of the presence of another cell type surrounding the growing cell population, the effect of mutations and the critical surface dynamics of monolayers. Different from unstructured cell populations, cells in early development and at tissue interfaces usually form highly organized structures. An example are tissue layers. Under certain circumstances such layers are observed to fold. We show that folding pattern again can largely be explained by physical mechanisms either by a buckling instability or active cell shape changes. The paper combines new and published material and aims at an overview of a wide range of physical aspects in unstructured populations and growing tissue layers.