Synthetic Multicellular Systems for Spontaneous Pattern Formation

Abstract

Multicellular organisms present amazing examples of self-organized patterns. As a hallmark of the self-organization process, coordinated cellular behavior, commonly orchestrated at a population level, regulates the dynamic spatial arrangement of specialized cell types to generate tissue patterning and form complex body layout. Such coordination often relies on reciprocal interactions among different cell species during morphogenesis. However, the nature of the potential interaction and how such interaction can achieve coordinated spatial patterning and self-organization of multiple cell types still remain elusive. Here we describe a periodic stripe patterning process emerging from a synthetic multicellular system with programmed population interaction. The interaction enables coordinated out-of-phase spatial oscillation of cell densities of two engineered populations of Escherichia Coli. Such pattern arises autonomously from reciprocal density-dependent activation of mobility between the two cell species independent of any preexisting positional cues. Moreover, by manipulating the interaction, the original out-of-phase spatial oscillation rhythm can be accordingly turned into in-phase oscillation. The occurrences of out-of-phase and in-phase spatial oscillating patterns suggest density-dependent control of mobility as a simple and general strategy for spatial patterning of run-and-tumble cells even when multiple cell species (over two) were incorporate in the synthetic systems.