A synthetic multi-cellular network of coupled self-sustained oscillators.

Journal: PloS one
Published Date:

Abstract

Engineering artificial networks from modular components is a major challenge in synthetic biology. In the past years, single units, such as switches and oscillators, were successfully constructed and implemented. The effective integration of these parts into functional artificial self-regulated networks is currently on the verge of breakthrough. Here, we describe the design of a modular higher-order synthetic genetic network assembled from two independent self-sustained synthetic units: repressilators coupled via a modified quorum-sensing circuit. The isolated communication circuit and the network of coupled oscillators were analysed in mathematical modelling and experimental approaches. We monitored clustering of cells in groups of various sizes. Within each cluster of cells, cells oscillate synchronously, whereas the theoretical modelling predicts complete synchronization of the whole cellular population to be obtained approximately after 30 days. Our data suggest that self-regulated synchronization in biological systems can occur through an intermediate, long term clustering phase. The proposed artificial multicellular network provides a system framework for exploring how a given network generates a specific behaviour.

Authors

  • Miguel Fernández-Niño
    Departamento de Biología, Universidad Nacional de Colombia, Bogotá, Colombia.
  • Daniel Giraldo
    Grupo de Diseño de Productos y Procesos (GDPP), Departamento de Ingeniería Química, Universidad de los Andes, Bogotá DC, Colombia.
  • Judith Lucia Gomez-Porras
    Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile.
  • Ingo Dreyer
    Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile.
  • Andrés Fernando González Barrios
    Grupo de Diseño de Productos y Procesos (GDPP), Departamento de Ingeniería Química, Universidad de los Andes, Bogotá DC, Colombia.
  • Catalina Arevalo-Ferro
    Departamento de Biología, Universidad Nacional de Colombia, Bogotá, Colombia.