Mechanically-driven phase separation in a growing bacterial colony

Abstract

Secretion of extracellular polymeric substances (EPSs) by growing bacteria is an integral part of forming biofilm-like structures. In such dense systems, mechanical interactions among the structural components can be expected to significantly contribute to morphological properties. Here, we use a particle-based modeling approach to study the self-organization of nonmotile rod-shaped bacterial cells growing on a solid substrate in the presence of selfproduced EPSs. In our simulation, all of the components interact mechanically via repulsive forces, occurring as the bacterial cells grow and divide (via consuming diffusing nutrient) and produce EPSs. Based on our simulation, we show that mechanical interactions control the collective behavior of the system. In particular, we find that the presence of nonadsorbing EPSs can lead to spontaneous aggregation of bacterial cells by a depletion attraction and thereby generates phase separated patterns in the nonequilibrium growing colony. Both repulsive interactions between cell and EPSs and the overall concentration of EPSs are important factors in the self-organization in a nonequilibrium growing colony. Furthermore, we investigate the interplay of mechanics with the nutrient diffusion and consumption by bacterial cells and observe that suppression of branch formation occurs due to EPSs compared with the case where no EPS is produced.A common underlying theme of biophysics of living matter is the quest to understand how local interactions of individual components lead to collective behavior and formation of highly self-organized systems (1-6). In this regard, bacterial systems are an especially interesting example. Bacteria are known to selforganize into multicellular communities, commonly known as biofilms, in which microbial cells live in close association with a solid surface or liquid-air interface and are embedded in a self-produced extracellular matrix. Extracellular polymeric substances (EPSs) play an important role in determining the structural and mechanical architecture of a biofilm (7-12). Generally, the collective dynamics of bacterial colony involves a complex interplay of various physical, chemical, and biological mechanisms, such as growth and differentiation of cells, production of EPSs, the collective movement of cells determined by interacting physical forces and chemical cues, e.g., chemotaxis, motility, cellcell signaling, adhesion, and gene regulation (13)(14)(15)(16)(17)(18)(19). At low density, communication among cells occurs mainly through chemical signals (20). However, at a higher density, as bacteria aggregate and form dense communities, direct mechanical interaction becomes increasingly relevant in the self-organization (21-23). In this regard, microfluidics-based experiments coupled with continuum modeling of cellular dynamics by Volfson et al.(24) was a pioneering study emphasizing the role of cell-cell mechanical interaction in the growth of a highly organized bacterial colony. As a significant extension, Farrell and coworkers (25, 26) hav...

Architectural transitions in Vibrio cholerae biofilms at single-cell resolution

“…Internal and global biofilm architectures are presumably consequences of emergent interactions between individual cell growth, physiological differentiation, secreted proteins, polymers and small molecules, and microenvironmental heterogeneity (21,(26)(27)(28)(29)(30)(31)(32)(33)(34). Attempts to dissect the individual and combined contributions of these factors to biofilm growth have increasingly relied on examination of bacterial communities in microfluidic devices that mimic central features of natural environments (11,35,36).…”

Spreading of nonmotile bacteria on a hard agar plate: Comparison between agent-based and stochastic simulations

“…These interactions can arise from mechanical forces exerted by bacteria as they grow, divide and push each other and spread on a hard substrate. How individual interactions turn out to be significant in forming collective orders, have been explored successfully by using agent based models in some of the earlier studies [29][30][31]. Ref.…”

“…Recently, in Ref. [31] mechanical-driven spontaneous phase-segregation of nonmotile, rodshaped bacteria and in presence of self-secreted extracellular polymeric substances in a growing biofilm has been explored using an agent-based model.…”

Emergent pattern formation in an interstitial biofilm

“…In parallel, biophysical models of non-motile bacteria have shown how the physical interactions between growing cells and the soft material surrounding them can determine group morphology [7][8][9].…”