Recent studies showed, experimentally, that localized cell death triggers the formation of wrinkles in Bacillus subtilis biofilms . These studies suggest that the main effect of cell death is to break adhesive interactions between cells and the supporting agarose substratum, changing the spatial distribution of mechanical stresses in the interior of colony. The formation of wrinkles result in a reduction of the effective mechanical stress inside the biofilm. We used Biocellion to developed a simple model of the process of wrinkle formation triggered by localized cell death, focusing on the mechanical interactions inside the colony. Details of the model can be found in our article published in PLOS One .
We setup an initial configuration in which cells are placed randomly in a regular box, see Figure. Cells are modeled by spheres of radius 4.125 micrometers which remains constant during the simulation. The mechanical interactions are modeled by setting up elastic bonds (implemented as junctions in Biocellion) between cells and between cells and the agarose substratum. Cell death is then modelled by removing the cells with centers located in the volumetric region of the cell death pattern (CDP) at the colony-substratum interface, depicted as a empty rectangle in the bottom of the colony, see Figure.
After 10000 simulation steps, a wrinkle is formed at the top of the area of cell death as shown in the Video and in the Figure, in which cells are colored according to the hydrostatic pressure supported by the cells, red for compression and blue for tension. This simulation shows how the cell deah generates an heterogeneous distribution of mechanical stress, which drive the cells towards the center of the colony and subsequently the formation of a wrinkle. Although this is not a comprehensive model of wrinkle formation in biofilms, this example shows the potential of the proposed framework to study the role of mechanical interactions on the morphogenesis of biofilms.
- Asally, M., Kittisopikul, M., et al. (2012). Localized cell death focuses mechanical forces during 3D patterning in a biofilm. PNAS, 109, no. 46, 18891-18896.
- Aguilar, B., Ghaffarizadeh, A., et al. (2018). Cell death as a trigger for morphogenesis. PLOS One.