Session B13: Cells as active matter modifying their environment: from colloids to cancer

Emergent behavior driven by self-generated gradients: from active droplets to bacterial suspension

The out-of-equilibrium dynamics of chemotactic active matter—be it animate or inanimate—is coupled to the environment which is a chemical landscape constantly modified by secretions from the motile agents, nutrient consumption, or respiration. This can give rise to complex collective dynamics, altering the migration strategies or pattern formation by the active agents.

In this talk, I will first discuss self-propelling droplets as a model for chemically active particles that modify their environment by leaving chemical footprints, which act as chemorepulsive signals to other droplets. I will present our analysis of this communication mechanism quantitatively both on the scale of individual agent–trail collisions as well as on the collective scale where droplets actively remodel their environment while adapting their dynamics to that evolving chemical landscape. We show in experiment and simulation how these interactions cause a transient dynamical arrest in active emulsions where swimmers are caged between each other’s trails of secreted chemicals. These findings yield principles for predicting how negative autochemotaxis shapes the navigation strategy of chemically active particles.

Next, I will discuss the dynamics of aerobic bacterial suspensions that are confined in tight spots where oxygen availability is spatially variable. In such systems, the cellular motility is coupled to the local oxygen concentration. We show that bacteria collectively consume oxygen, generate an oxygen gradient, and then respond to it by separating into two distinct aerobic and anaerobic phases.

    

The collective movement of chemotactic bacterial cells along self-generated gradients

Many cell populations actively move depending on environmental conditions which they shape themselves. Populations of chemotactic bacteria, for example, commonly coordinate their movement to reach new nutrient sources. The movement is driven by a combination of flagella-driven propulsion along sensed gradients in nutrient availability and the consumption of nutrients which shape these gradients. I discuss in this talk recent progress in understanding this navigated migration process and the cell-physiological and environmental factors which shape it. First, I present theory and experiments with the model organism E. coli which show how bacterial populations can utilize chemotaxis and substrate consumption to rapidly migrate into nutrient-rich territory. I contrast these migration dynamics to those modeled by the Fisher-Kolmogorov-Petrovsky-Piskunov equation which which do not include chemotaxis and are canonically used to describe the migration of motile organisms into new territories. Second, I discuss how E. coli cells tightly couple the synthesis and activity of their motility machinery with biomass accumulation and cell size to ensure efficient swimming and rapid migration across a wide range of environmental conditions. Third, I outline how E. coli might utilize chemotaxis and navigated migration via self-generated nutrient gradients to thrive within their native habitat of the mammalian intestine. Finally, I argue why the discussed navigated form of migration, enabled by chemotaxis and a strong impact of cells on their local environment, could be ubiquitous and drive the collective movement of many cell types across biological domains.   

Understanding the emergence of microbial collective behaviors in the wild

Groups of cells generate large-scale behaviors and form patterns over vastly larger scales than individuals can sense, making them a classic type of active matter. A fundamental problem in understanding natural active matter is that their activities take place in highly complex, heterogeneous environments. In the case of cells, these environments affect both how the individual cellular agents coordinate and the movement behaviors they exhibit. A classic form of active cellular matter is cellular slime molds, which after starvation use a biochemical environmental signal to coordinate aggregation into multicellular groups. Existing models capture how on flat, homogenous substrates this signal relay produces emergent, population-wide spiral waves that lead cells to aggregate. However, this behavior evolved in complex, three dimensional environments like soil. We have designed a naturalistic environmental system where we can quantify how cellular changes such as number and density and environmental features such as particle size perturb collective outcomes. By capturing the aggregation process in these transparent soil microcosms, we aim to explore two fundamental questions: (1) how do features of the environment, together with individual properties, shape collective outcomes? and (2) what allows collective behaviors to be robust to environmental heterogeneity?   

How amoeboid cells can modify their environment and can coordinate their motion

Collective cell migration plays an important role in many biological processes such as development, wound healing and cancer metastasis. In this talk, we will focus on the collective migration of Dictyostelium discoideum cells, a social amoeba. Upon starvation, and as part of a survival mechanism, these cells aggregate into large clusters, requiring robust coordination of signaling and motion. We will present two examples how experiments and modeling can shed light on this coordination. First, we will show that small aggregates of Dictyostelium can show dispersal behavior during which cells are moving away from, instead of towards, the aggregate. Using a combination of experiments and modeling, we show that this dispersal can arise due to a competition between the diffusible chemoattractant and the enzyme that degrades it. The latter modifies the environment such that the chemoattractant gradient near the aggregate can change sign. Second, we present results on vertically constrained aggregates in which cells rotate in a collective manner. We quantify the forces exerted on the substrate by the cells using traction force microscopy and visualize the chemoattractant signaling using fluorescent microscopy. Using modeling, we show that the interaction between signaling and motion can explain the observed traction force patterns.