Dissecting the physics of bacterial biofilms with agent-based simulations

Biofilms are surface-attached bacterial communities encased within extracellular matrices (ECMs) of biopolymers that play many significant roles in health and society. Biofilms are versatile, living biomaterials that are resilient to a wide range of external perturbations, primarily due to the ECM, which consists of a complex network of polymeric macromolecules. Newly established platforms for live biofilm imaging at single-cell resolution have revealed a wealth of novel insights into the emergence of cellular organization within a developing biofilm. This has, in turn, necessitated the development of modeling approaches that can pinpoint the mechanistic origins of this organization. In this review, we discuss the use of agent-based models (ABMs) as a general framework for simulating the development of bacterial colonies and biofilms. We describe the ingredients that are typically included in an ABM, together with the biological entity or process that each such ingredient represents, and the assumptions that underlie its precise formulation within the model. We then discuss a selection of recent studies in which ABMs have been used to investigate the physical mechanisms that govern biofilm development, focusing on our recent work on orientational ordering within Vibrio cholerae biofilms. Finally, we describe the numerous ways in which we foresee that ABMs can be leveraged to further our understanding of biofilm development.