Vedel, Søren1; Tay, Savas4; Johnston, Darius M.5; Bruus, Henrik2; Quake, Stephen R.6
1 Department of Micro- and Nanotechnology, Technical University of Denmark2 Department of Physics, Technical University of Denmark3 Biophysics and Fluids, Department of Physics, Technical University of Denmark4 Eidgenössische Technische Hochschule5 unknown6 Stanford University
In multicellular organisms and complex ecosystems, cells migrate in a social context. While this is essential for the basic processes of life such as embryonic development, wound healing and unregulated migration furthermore is implicated in diseases such as cancer, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has revealed a stereotypical migratory behavior, however many aspects of the migration characteristics of cells in populations remained unknown exactly because of this lack of characterization of neighbour-cell influence. We quantified1 the migration of thousands of individual cells in their population context using time-lapse microscopy, microfluidic cell culture and automated image analysis, and discovered a much richer dynamics in the social context, with significant variations in directionality, displacement and speed, which are all modulated by the local cell density. We developed a mathematical model based on the experimentally identified ‘‘cellular traffic rules’’, previous knowledge from isolated-cell chemotaxis and Newton’s second law, which revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, with the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how complex biology can be explained by simple rules of physics, and comprises a test-bed for future studies of collective migration of individual cells.