TY - JOUR T1 - Computational model of fractal interface formation in bacterial biofilms JF - bioRxiv DO - 10.1101/2022.05.10.491419 SP - 2022.05.10.491419 AU - Caelan Brooks AU - Jake T. McCool AU - Alan Gillman AU - Gürol M. Süel AU - Andrew Mugler AU - Joseph W. Larkin Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/05/10/2022.05.10.491419.abstract N2 - Bacterial colonies benefit from cellular heterogeneity, with cells differentiating into diverse states of physiology and gene expression. As colonies grow, such cells in distinct states arrange into spatial patterns. To uncover the functional role of these emergent patterns, we must understand how they arise from cellular growth, phenotypic inheritance, and mechanical interactions among cells. Here we present a simple, agent-based model to predict patterns formed by motile and extracellular matrix-producing cells in developing populations of Bacillus subtilis bacteria. By incorporating phenotypic inheritance, differential mechanical interactions of the two cell types, and the escape of peripheral motile cells, our model predicts the emergence of a pattern: matrix cells surround a fractal-like population of interior motile cells. We find that, while some properties of the emergent motile-matrix interface depend on the initial spatial arrangement of cells, the distribution of motile cells at large radii are a product solely of the model’s growth mechanism. Using a box-counting analysis, we find that the emergent motile-matrix interface exhibits a fractal dimension that increases as biofilms grow but eventually reaches a maximum as the thickness of the peripheral layer of matrix exceeds the capacity of the inner cells to push matrix cells out of the way. We find that the presence of the fractal interface correlates with a larger colony growth rate and increases the local proximity of motile and matrix cells, which could promote resource sharing. Our results show that simple computational models can account for morphological features of active systems like bacterial colonies, where colony-level phenotypes emerge from single cell-level properties and cells modifying their own environment.Author summary Like cells in our bodies, bacterial cells can differentiate into different cell types, which perform different roles in colonies. During the growth of Bacillus subtilis colonies, motile cells, which can swim, and matrix cells, which produce sticky polymers to adhere cells together, form reproducible spatial patterns. Multiple factors could drive the formation of these patterns, including inheritance of the motility and matrix states as cells divide, and different mechanical interactions between different cell types as they push each other around during growth. We created an agent-based computational model, in which we represent bacterial cells as occupying squares within a grid. We find that through inheritance of motile and matrix state and greater resistance to physical pushing by matrix cells, our model produces patterns similar to those observed in experiments—an exterior population of matrix cells surrounding an interior group of motile cells with fractal arms that branch into the outer matrix layer. Our results show that simple models can account for complex phenomena like the growth of heterogeneous bacterial colonies.Competing Interest StatementAlan Gillman is an employee of Evident Scientific. ER -