Microorganisms often live in dense, surface-attached communities called biofilms. These biofilms exist in diverse environments, from the inside of your gut and the surfaces of your teeth, to the roots of your house plants and the inside of your coffee machine. These biofilms, composed of various bacteria, fungi, and viruses encased in a self-produced extracellular matrix, exhibit complex behaviours. They also play a dual role in human health and industry, contributing to persistent infections and antibiotic resistance while being crucial for digestion and industrial applications like wastewater treatment. Understanding biofilm formation and function is essential for decreasing their detrimental effects and increasing their potential in biotechnology.
In this thesis, I use individual-based modelling of spherocylindrical particles to learn something about the effects of spatial structure on their mechanical and social interactions.
In chapter 2 we explore the aggregation dynamics of blue-light switchable adhesive E. coli in solution. We aim to understand experimental results that bacteria aggregate more and formed bigger clusters under pulsating light. We simulate a system of particles undergoing Brownian motion, where the cell-cell adhesion can be periodically turned on and off and compare and match our simulations to the experimental data. We show how tuning the light off-period to the decay time of the adhesion leads to increased clustering. We conclude that partial disassembly of the aggregates leads to more effective clustering. In addition, our co-authors show that this increased clustering leads to increased biofilm formation in a laboratory setting. Moreover, it can be used to increase productivity in a bioreactor.
We use what we learnt about cell-cell interactions to simulate growing surface attached systems in chapter 3. We motivate some choices about the interactions between cells and the interaction with the surface. We then show how varying the strengths of these interactions can lead to different microcolony architectures.
We then use this model of growing microcolonies to study cooperator interactions in a spatially structured environment. Where the mechanical interactions occur over short distances, we also assume that metabolic interactions are close range. In chapter 4, we simulate a cross-feeding consortium in the presence of a cheater species by having particles adjust their growth rate based on the cells in their immediate environment. Using simulations and an experimental consortium, we show how the time it takes for cooperators to meet is the determining factor in whether they outcompete their cheating counterparts.
Finally, in chapter 5 we explore the patterning that cooperating particles create by mixing. We show that this cooperator mixing is mostly determined by interaction strength and is robust against variations in size and interaction symmetry. Additionally, we show that in the presence of cheaters, cooperators intermix but cheaters don’t mix with the cooperators and instead remain on the outside. Therefore, we argue that focusing on strong cooperation is a great strategy for cheater exclusion.
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The transition of bacteria from an individualistic to a biofilm lifestyle profoundly alters their biology. During biofilm development, the bacterial cell-cell adhesions are a major determinant of initial microcolonies, which serve as kernels for the subsequent microscopic and mesoscopic structure of the biofilm, and determine the resulting functionality. In this study, the significance of bacterial cell-cell adhesion dynamics on bacterial aggregation and biofilm maturation is elucidated. Using photoswitchable adhesins between bacteria, modifying the dynamics of bacterial cell-cell adhesions with periodic dark-light cycles is systematic. Dynamic cell-cell adhesions with liquid-like behavior improve bacterial aggregation and produce more compact microcolonies than static adhesions with solid-like behavior in both experiments and individual-based simulations. Consequently, dynamic cell-cell adhesions give rise to earlier quorum sensing activation, better intermixing of different bacterial populations, improved biofilm maturation, changes in the growth of cocultures, and higher yields in fermentation. The here presented approach of tuning bacterial cell-cell adhesion dynamics opens the door for regulating the structure and function of biofilms and cocultures with potential biotechnological applications.

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