A competitive advantage through fast dead matter elimination in confined cellular aggregates

Abstract

Competition of different species or cell types for limited space is relevant in a variety of biological processes such as biofilm development, tissue morphogenesis and tumor growth. Predicting the outcome for non-adversarial competition of such growing active matter is non-trivial, as it depends on how processes like growth, proliferation and the degradation of cellular matter are regulated in confinement; regulation that happens even in the absence of competition to achieve the dynamic steady state known as homeostasis. Here, we show that passive by-products of the processes maintaining homeostasis can significantly alter fitness. Even for purely pressure-regulated growth and exclusively mechanical interactions, this enables cell types with lower homeostatic pressure to outcompete those with higher homeostatic pressure. We reveal that interfaces play a critical role for this specific kind of competition: There, growing matter with a higher proportion of active cells can better exploit local growth opportunities that continuously arise as the active processes keep the system out of mechanical equilibrium. We elucidate this effect in a theoretical toy model and test it in an agent-based computational model that includes finite-time mechanical persistence of dead cells and thereby decouples the density of growing cells from the homeostatic pressure. Our results suggest that self-organization of cellular aggregates into active and passive matter can be decisive for competition outcomes and that optimizing the proportion of growing (active) cells can be as important to survival as sensitivity to mechanical cues.

Morphological instability and roughening of growing 3D bacterial colonies

“…More broadly, given our finding of morphological instability and roughening that emerge generically from the coupling between diffusion and uptake of essential substrates for cellular growth in 3D, we expect that similar behavior could arise in other growing systems, with implications for the evolution of form and function ( 50 , 58 , 140 – 142 ). Indeed, similar 3D patterns of rough growth have been observed in other living systems, namely in multicellular clusters of Saccharomyces cerevisiae , usually referred to as “snowflake yeast,” or in aggregation clusters of the green alga Volvox carteri .…”

“…To rationalize the experimental observations and test our hypothesis regarding the morphological instability and roughening, we model a densely packed growing bacterial colony embedded in a 3D hydrogel by means of a continuum theory, where bacteria are treated as an active fluid whose expansion is driven by substrate-dependent growth; here, we use the term “active” to reflect the process of cellular growth. Similar approaches were used to model growing bacterial colonies in other settings ( 28 , 31 , 32 , 37 , 39 , 50 , 73 ) as well as other biological morphodynamics ( 94 – 100 ). In Fig.…”

“…These morphologies are now understood to arise from friction between the growing colony and the surface and differential access to nutrients, which may also be available from the third dimension ( 13 – 18 , 20 , 22 – 26 ). The emergent patterns have been rationalized by incorporating these key ingredients into reaction–diffusion equations ( 14 – 16 , 18 , 22 , 27 – 36 ), active continuum theories ( 19 – 21 , 28 , 31 , 37 – 53 ), and agent-based models ( 28 , 31 , 38 , 40 , 45 , 46 , 54 – 57 ). Moreover, it has been suggested that these growth patterns may, in turn, influence the global function and physiology of bacterial colonies ( 58 – 60 ), including resistance to antibiotics ( 61 – 63 ) and parasites ( 64 ), resilience to environmental changes ( 65 , 66 ), and genetic diversity ( 56 , 58 , 59 , 67 – 73 ).…”

Instabilities in a growing system of active particles: scalar and vectorial systems

“…1,2 Bacterial colonies, [3][4][5] biofilms, [6][7][8] and growing tissues [9][10][11][12] are standard examples that belong to the class of active systems where one can study the growth phenomena. Along this general task, self-organization and ordering in active colonies, [13][14][15][16][17][18] pattern formation in biological systems 13,19,20 and nematic ordering in bacterial colonies 21,22 are studied extensively.…”

Stress anisotropy in confined populations of growing rods

“…It constitutes another process by which energy can be injected into the system at the microscopic scale and has been shown to be able to balance out chemical interactions at the level of large-scale behaviour [8]. The mechanisms by which growing active matter self-organizes to form multicellular communities such as biofilms [9,10] and functioning tissues [11][12][13] are complex and often involve other forms of activity or internal regulation [14][15][16][17]. Here, we focus on the mechanical aspects of growth, mediated by steric interactions between individual rod-shaped cells and confinement.…”