Bioelectric stimulation controls tissue shape and size.

Epithelial tissues sheath organs and electro-mechanically regulate ion and water transport to regulate development, homeostasis, and hydrostatic organ pressure. Here, we demonstrate how external electrical stimulation allows us to control these processes in living tissues. Specifically, we electrically stimulate hollow, 3D kidneyoids and gut organoids and find that physiological-strength electrical stimulation of ∼ 5 - 10 V/cm powerfully inflates hollow tissues; a process we call electro-inflation. Electro-inflation is mediated by increased ion flux through ion channels/transporters and triggers subsequent osmotic water flow into the lumen, generating hydrostatic pressure that competes against cytoskeletal tension. Our computational studies suggest that electro-inflation is strongly driven by field-induced ion crowding on the outer surface of the tissue. Electrically stimulated tissues also break symmetry in 3D resulting from electrotaxis and affecting tissue shape. The ability of electrical cues to regulate tissue size and shape emphasizes the role and importance of the electrical micro-environment for living tissues.

The fluidic memristor as a collective phenomenon in elastohydrodynamic networks.

Fluid flow networks are ubiquitous and can be found in a broad range of contexts, from human-made systems such as water supply networks to living systems like animal and plant vasculature. In many cases, the elements forming these networks exhibit a highly non-linear pressure-flow relationship. Although we understand how these elements work individually, their collective behavior remains poorly understood. In this work, we combine experiments, theory, and numerical simulations to understand the main mechanisms underlying the collective behavior of soft flow networks with elements that exhibit negative differential resistance. Strikingly, our theoretical analysis and experiments reveal that a minimal network of nonlinear resistors, which we have termed a 'fluidic memristor', displays history-dependent resistance. This new class of element can be understood as a collection of hysteresis loops that allows this fluidic system to store information, and it can be directly used as a tunable resistor in fluidic setups. Our results provide insights that can inform other applications of fluid flow networks in soft materials science, biomedical settings, and soft robotics, and may also motivate new understanding of the flow networks involved in animal and plant physiology.

Interfacial morphodynamics of proliferating microbial communities.

In microbial communities, various cell types often coexist by occupying distinct spatial domains. What determines the shape of the interface between such domains-which in turn influences the interactions between cells and overall community function? Here, we address this question by developing a continuum model of a 2D spatially-structured microbial community with two distinct cell types. We find that, depending on the balance of the different cell proliferation rates and substrate friction coefficients, the interface between domains is either stable and smooth, or unstable and develops finger-like protrusions. We establish quantitative principles describing when these different interfacial behaviors arise, and find good agreement both with the results of previous experimental reports as well as new experiments performed here. Our work thus helps to provide a biophysical basis for understanding the interfacial morphodynamics of proliferating microbial communities, as well as a broader range of proliferating active systems.

Pattern formation by bacteria-phage interactions.

The interactions between bacteria and phages-viruses that infect bacteria-play critical roles in agriculture, ecology, and medicine; however, how these interactions influence the spatial organization of both bacteria and phages remain largely unexplored. Here, we address this gap in knowledge by developing a theoretical model of motile, proliferating bacteria that aggregate via motility-induced phase separation (MIPS) and encounter phage that infect and lyse the cells. We find that the non-reciprocal predator-prey interactions between phage and bacteria strongly alter spatial organization, in some cases giving rise to a rich array of finite-scale stationary and dynamic patterns in which bacteria and phage coexist. We establish principles describing the onset and characteristics of these diverse behaviors, thereby helping to provide a biophysical basis for understanding pattern formation in bacteria-phage systems, as well as in a broader range of active and living systems with similar predator-prey or other non-reciprocal interactions.

Morphological instability and roughening of growing 3D bacterial colonies.

How do growing bacterial colonies get their shapes? While colony morphogenesis is well studied in two dimensions, many bacteria grow as large colonies in three-dimensional (3D) environments, such as gels and tissues in the body or subsurface soils and sediments. Here, we describe the morphodynamics of large colonies of bacteria growing in three dimensions. Using experiments in transparent 3D granular hydrogel matrices, we show that dense colonies of four different species of bacteria generically become morphologically unstable and roughen as they consume nutrients and grow beyond a critical size-eventually adopting a characteristic branched, broccoli-like morphology independent of variations in the cell type and environmental conditions. This behavior reflects a key difference between two-dimensional (2D) and 3D colonies; while a 2D colony may access the nutrients needed for growth from the third dimension, a 3D colony inevitably becomes nutrient limited in its interior, driving a transition to unstable growth at its surface. We elucidate the onset of the instability using linear stability analysis and numerical simulations of a continuum model that treats the colony as an "active fluid" whose dynamics are driven by nutrient-dependent cellular growth. We find that when all dimensions of the colony substantially exceed the nutrient penetration length, nutrient-limited growth drives a 3D morphological instability that recapitulates essential features of the experimental observations. Our work thus provides a framework to predict and control the organization of growing colonies-as well as other forms of growing active matter, such as tumors and engineered living materials-in 3D environments.

Membrane fission during bacterial spore development requires cellular inflation driven by DNA translocation.

Bacteria require membrane fission for both cell division and endospore formation. In Bacillus subtilis, sporulation initiates with an asymmetric division that generates a large mother cell and a smaller forespore that contains only a quarter of its genome. As the mother cell membranes engulf the forespore, a DNA translocase pumps the rest of the chromosome into the small forespore compartment, inflating it due to increased turgor. When the engulfing membrane undergoes fission, the forespore is released into the mother cell cytoplasm. The B. subtilis protein FisB catalyzes membrane fission during sporulation, but the molecular basis is unclear. Here, we show that forespore inflation and FisB accumulation are both required for an efficient membrane fission. Forespore inflation leads to higher membrane tension in the engulfment membrane than in the mother cell membrane, causing the membrane to flow through the neck connecting the two membrane compartments. Thus, the mother cell supplies some of the membrane required for the growth of the membranes surrounding the forespore. The oligomerization of FisB at the membrane neck slows the equilibration of membrane tension by impeding the membrane flow. This leads to a further increase in the tension of the engulfment membrane, promoting its fission through lysis. Collectively, our data indicate that DNA translocation has a previously unappreciated second function in energizing the FisB-mediated membrane fission under energy-limited conditions.

Cellular Sensing Governs the Stability of Chemotactic Fronts.

In contexts ranging from embryonic development to bacterial ecology, cell populations migrate chemotactically along self-generated chemical gradients, often forming a propagating front. Here, we theoretically show that the stability of such chemotactic fronts to morphological perturbations is determined by limitations in the ability of individual cells to sense and thereby respond to the chemical gradient. Specifically, cells at bulging parts of a front are exposed to a smaller gradient, which slows them down and promotes stability, but they also respond more strongly to the gradient, which speeds them up and promotes instability. We predict that this competition leads to chemotactic fingering when sensing is limited at too low chemical concentrations. Guided by this finding and by experimental data on E. coli chemotaxis, we suggest that the cells' sensory machinery might have evolved to avoid these limitations and ensure stable front propagation. Finally, as sensing of any stimuli is necessarily limited in living and active matter in general, the principle of sensing-induced stability may operate in other types of directed migration such as durotaxis, electrotaxis, and phototaxis.

Fingering instability in spreading epithelial monolayers: roles of cell polarisation, substrate friction and contractile stresses.

Collective cell migration plays a crucial role in many developmental processes that underlie morphogenesis, wound healing, or cancer progression. In such coordinated behaviours, cells are organised in coherent structures and actively migrate to serve different biological purposes. In some contexts, namely during epithelial wound healing, it is well known that a migrating free-edge monolayer develops finger-like instabilities, yet the onset is still under debate. Here, by means of theory and numerical simulations, we shed light on the main mechanisms driving the instability process, analysing the linear and nonlinear dynamics of a continuum compressible polar fluid. In particular, we assess the role of cell polarisation, substrate friction, and contractile stresses. Linear theory shows that it is crucial to analyse the perturbation transient dynamics, since we unravel a plethora of crossovers between different exponential growth rates during the linear regime. Numerical simulations suggest that cell-substrate friction could be the mechanism responsible for the formation of complex finger-like structures at the edge, since it triggers secondary fingering instabilities and tip-splitting phenomena. Finally, we obtain a critical contractile stress that depends on cell-substrate friction and the initial-to-nematic length ratio, characterising an active wetting-dewetting transition. In the dewetting scenario, the monolayer retracts and becomes stable without developing finger-like structures.

FisB relies on homo-oligomerization and lipid binding to catalyze membrane fission in bacteria.

Little is known about mechanisms of membrane fission in bacteria despite their requirement for cytokinesis. The only known dedicated membrane fission machinery in bacteria, fission protein B (FisB), is expressed during sporulation in Bacillus subtilis and is required to release the developing spore into the mother cell cytoplasm. Here, we characterized the requirements for FisB-mediated membrane fission. FisB forms mobile clusters of approximately 12 molecules that give way to an immobile cluster at the engulfment pole containing approximately 40 proteins at the time of membrane fission. Analysis of FisB mutants revealed that binding to acidic lipids and homo-oligomerization are both critical for targeting FisB to the engulfment pole and membrane fission. Experiments using artificial membranes and filamentous cells suggest that FisB does not have an intrinsic ability to sense or induce membrane curvature but can bridge membranes. Finally, modeling suggests that homo-oligomerization and trans-interactions with membranes are sufficient to explain FisB accumulation at the membrane neck that connects the engulfment membrane to the rest of the mother cell membrane during late stages of engulfment. Together, our results show that FisB is a robust and unusual membrane fission protein that relies on homo-oligomerization, lipid binding, and the unique membrane topology generated during engulfment for localization and membrane scission, but surprisingly, not on lipid microdomains, negative-curvature lipids, or curvature sensing.