Flow-induced symmetry breaking in growing bacterial biofilms

Abstract

Bacterial biofilms are matrix-bound multicellular communities. Biofilms represent a major form of microbial life on Earth and serve as a model active nematic system, in which activity results from growth of the rod-shaped bacterial cells. In their natural environments, from human organs to industrial pipelines, biofilms have evolved to grow robustly under significant fluid shear. Despite intense practical and theoretical interest, it is unclear how strong fluid flow alters the local and global architectures of biofilms. Here, we combine highly time-resolved single-cell live imaging with 3D multi-scale modeling to investigate the effects of flow on the dynamics of all individual cells in growing biofilms. Our experiments and cell-based simulations reveal that, in the initial stages of development, the flow induces a downstream gradient in cell orientation, causing asymmetrical droplet-like biofilm shapes. In the later stages, when the majority of cells are sheltered from the flow by the surrounding extracellular matrix, buckling-induced cell verticalization in the biofilm core restores radially symmetric biofilm growth, in agreement with predictions from a 3D continuum model.

Emergent robustness of bacterial quorum sensing in fluid flow

“…As such, the fluid flow imparts a shear stress (which may vary in space and time) to the upper boundary of the cell layer. We neglect growthinduced flows inside the cell layer because their timescales are typically much slower than those of diffusion and external flow [18,42].…”

“…Fluid flow is ubiquitous in a diverse range of bacterial habitats from rivers, lakes, and medical devices to the host teeth, gut, lungs, and nasal cavity [14]. In addition to its mechanical effects on the structure of cell populations [15][16][17][18][19], external fluid flow has been found to have a strong influence on the transport of relevant chemicals including nutrients [8,20], antibiotics during host treatment [21,22], and QS autoinducers [23][24][25][26]. Recent experimental [23][24][25][26][27] and numerical [28][29][30][31][32][33][34] studies suggest that flow-induced autoinducer transport can affect population-level phenotypes by introducing chemical gradients within populations and, if the flow is strong enough, suppressing QS altogether.…”

Multicellular and unicellular responses of microbial biofilms to stress

“…Mechanical shear stress on biofilms that are grown in the presence of flow primarily affects cells on the flowexposed surface of the biofilm (Pearce et al 2019;Stewart 2012). On the inside of the biofilm, where there is typically no flow, the cells could potentially also sense the deformation of the entire biofilm if they could sense the deformation of the matrix (Dufrêne and Persat 2020;Persat et al 2015).…”

“…Stresses that span over spatial scales that are significantly larger than clonal cluster sizes are unlikely to be recognized as spatially varying stresses by bacteria. However, some stresses occur on spatial scales that are comparable to the bacterial cell size or clonal cluster size, such as mechanical shear stress on the exterior of biofilms, and gradients of nutrients within biofilms (Evans et al 2020;Flemming et al 2016;Pearce et al 2019;Serra and Hengge 2014;Stewart and Franklin, 2008). Such spatiallyorganized stress patterns that arise during biofilm growth are a characteristic feature of biofilms, and may be partly responsible for the emergent properties and benefits that cells obtain within biofilms.…”

Morphogenesis and cell ordering in confined bacterial biofilms

“…Biofilm formation is a morphogenetic process whereby a single founder cell develops into a three-dimensional aggregate in which bacterial cells interact with each other and with the environment (4)(5)(6)(7)(8). Recent work has revealed biophysical mechanisms underlying biofilm morphogenesis on solid substrates, which is controlled by cell-substrate adhesion and the resulting shear stress (9)(10)(11)(12)(13)(14)(15). In addition to those living on surfaces, bacterial communities are also commonly found inside soft, structured environments, such as hydrogels.…”