Agent-based Modeling for Biofilm Growth under Mechanical Confinement

Bacterial biofilm is a basic form of multicellular colonies grown on various surfaces. Mechanically confinement alters the morphological evolution and the collective cell ordering of a growing biofilm. Here we develop an agent-based model to elucidate the underlying biomechanical mechanisms of mechanically confined biofilm growth. The agent-based model quantitively reproduces density and morphology of biofilms from experiments under confinements of hydrogels of different stiffnesses. Large-scale agent-based simulations also provide 3D cell trajectories and the growth stress profiles in the growing biofilm as well as the hydrogels. A morphological transition occurs as hydrogel stiffness increasing, where radial alignment on the bottom surface and onion-like ordering on the top surface of biofilms emerges. As biofilm continues growing, the growth stress exceeds the cohesive strengths of the hydrogels or of the hydrogel-glass substrate, leading to fracture of the hydrogels or the hydrogel-glass interface and subsequently biofilm invasion into the fractured space. Our model highlights how mechanics shapes growing biofilms.