bioRxiv2025
In vitro colonies of the unicellular parasite Trypanosoma brucei expand radially and establish fingering instabilities, a collective behavior known as social motility. The underlying mechanisms are thought to involve single-cell motility, chemical communication among cells, and mechanical interactions with the liquid boundary, but their relative contributions remain unclear. We aimed to determine which of the mechanisms are necessary to quantitatively reproduce the morphological characteristics of social motility. We developed a two-dimensional agent-based model that simulates colonies of 105 - 106 cells at single-cell resolution--two to four orders of magnitude larger than previous models. Cells are represented as point particles executing directional random walks with auto-chemotactic alignment, combined with reflective and mutable boundaries and exponential colony growth. The model was quantitatively evaluated by applying our previously established morphology metrics. We show quantitative agreement of the simulation results and experimental data in terms of colony morphology. Parameter exploration revealed that finger formation arises within a narrow range of trypanosome motility parameters that balance stochasticity and alignment, while boundary conditions modulate the speed of colony expansion. The diffusion coefficient of the chemotactic signal is the key determinant of pattern formation. Realistic behavior occurs at 2x 10-11 - 10-10 m2/s which corresponds to molecules of 12.1-1690 kDa. These results demonstrate that complex colony morphologies can emerge from minimal cell-level rules, suggesting testable hypotheses for the molecular drivers of trypanosome social motility. Furthermore, our approach provides a framework for dissecting the interplay between motility, signaling, and mechanical confinement in other microbial systems exhibiting collective behavior. Author summaryIn vitro colonies of the unicellular parasite Trypanosoma brucei expand radially and form finger-like patterns, a behavior known as social motility. The ability of trypanosomes to exhibit social motility has been linked to their successful journey through their insect vector, the tsetse fly, which facilitates their survival and spreading between hosts. However, the mechanisms driving this behavior are not yet clear. Experimental data suggest that the movement and growth of individual cells, their interactions with each other, and their effects on colony boundaries may all play a role. These different factors are difficult to separate in experiments. We employed mathematical modeling to investigate the relative importance of these factors and developed a model that represents individual cells. The simulations reproduced finger formation patterns similar to those observed in experiments. The results show that complex colony shapes can emerge from simple cell behaviors. We also found that the speed at which a signaling chemical spreads between cells is crucial, and that the predicted values do not match the properties of the chemicals that have been proposed so far. Identifying and testing candidate signaling molecules in experiments could be the next step. Additionally, our approach may also aid in understanding collective behaviors in other microorganisms.