Biology subjects

Martinez-Calvo, A.

Publications and source records attributed to Martinez-Calvo, A..

10 recordsLinked to original sources

bioRxiv2026

Death & Chemotaxis: Bacterial chemotaxis enables collective escape from phage predation

Bacteriophages ("phage") are viruses that prey on bacteria in diverse environments, from biological tissues to soils. In many of these environments, bacterial hosts are constantly migrating, yet how bacterial migration is influenced by phage predation remains poorly understood. Using transparent granular hydrogels that mimic natural habitats, we directly visualize populations of motile Escherichia coli encountering lytic T4 phage. Unexpectedly, we find that even in phage-rich environments, bacteria successfully form chemotactic fronts that enable them to migrate over large distances without needing to develop phage resistance. Higher phage concentrations delay front formation but not steady-state front speed or shape. By combining our experiments with biophysical modeling, we demonstrate that this phenomenon arises from the ability of cells to collectively outrun trailing phage bursts--as quantified by a dimensionless "escape parameter" comparing chemotactic and predation rates. This work thus reveals and provides mechanistic insight into the role of cell motility in shaping phage-bacteria interactions in spatially-extended environments.

microbiology↗

bioRxiv2025

Kinase KEY1 controls pyrenoid condensate size throughout the cell cycle by disrupting phase separation interactions

Biomolecular condensates spatially organize cellular functions, but the regulation of their size, number, dissolution, and re-condensation is poorly understood. The pyrenoid, an algal biomolecular condensate that mediates one-third of global CO2 fixation, typically exists as one large condensate per chloroplast, but during cell division it transiently dissolves and reconfigures into multiple smaller condensates. Here, we identify a kinase, KEY1, in the model alga Chlamydomonas reinhardtii that regulates pyrenoid condensate size and number dynamics throughout the cell cycle and is necessary for normal pyrenoid function and growth. Unlike wild type, key1 mutant cells have multiple smaller condensates throughout the cell cycle that fail to dissolve during cell division. We show that KEY1 localizes to the condensates and promotes their dissolution by disrupting interactions between their core constituents, the CO2-fixing enzyme Rubisco and its linker protein EPYC1, through EPYC1 phosphorylation. We develop a biophysical model that recapitulates KEY1-mediated condensate size and number regulation and suggests a mechanism for controlling condensate position. These data provide a foundation for the mechanistic understanding of the regulation of size, number, position, and dissolution in pyrenoids and other biomolecular condensates.

cell biology↗

bioRxiv2025

Spatial self-organization of confined bacterial suspensions

Lab studies of bacteria usually focus on cells in spatially-extended, nutrient-replete settings, such as in liquid cultures and on agar surfaces. By contrast, many biological and environmental settings--ranging from mucus in the body to ocean sediments and the soil beneath our feet--feature multicellular bacterial populations that are confined to tight spots where essential metabolic substrates (e.g., oxygen) are scarce. What influence does such confinement have on a bacterial population? Here, we address this question by studying suspensions of motile Escherichia coli confined to quasi two-dimensional (2D) droplets. We find that when the droplet size and cell concentration are both large enough, the initially-uniform suspension spatially self-organizes into a concentrated, immotile inner "core" that coexists with a more dilute, highly-motile surrounding "shell". By simultaneously measuring cell concentration, oxygen concentration, and motility-generated fluid flow, we show that this behavior arises from the interplay between oxygen transport through the droplet from its boundary, uptake by the cells, and corresponding changes in their motility in response to oxygen variations. Furthermore, we use theory and simulations to develop quantitative principles describing this interplay--establishing a bio-physical framework that unifies all our experimental observations. Our work thereby sheds new light on the rich collective behaviors that emerge for bacterial populations, and other forms of chemically-reactive living and active matter, in confined environments, and provides a way to predict and control these behaviors more broadly.

biophysics↗

bioRxiv2024

Sticky enzymes: increased metabolic efficiency via substrate-dependent enzyme clustering

Coclustering of subsequent enzymes in a pathway can accelerate the processing of metabolic intermediates, with benefits including increased pathway fluxes, reduced toxicity, and sensitive branch-point regulation. While the optimal organization of such clusters has been explored theoretically, little is known about how to achieve such organization inside cells. Here we propose that phase-separating enzymes can self-organize into nearly-optimally sized and spaced clusters, provided that their "stickiness" is regulated by local substrate availability. In a nutshell, enzyme clusters only form when and where they are needed to process substrate. We study a mathematical model that implements this scheme for simple metabolic pathways, including all thermodynamic constraints. We find that pathway fluxes can be increased by 50 to 1000-fold and toxic metabolites can be decreased by 10 to 100-fold, at realistic enzyme densities. Finally, we discuss how enzyme "stickiness" could be allosterically regulated. This study presents a self-organization strategy that goes beyond current paradigms for natural and engineered enzyme clusters, and thus represents a motivating challenge to the fields of synthetic biology and metabolic engineering.

biophysics↗

bioRxiv2023

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.

biophysics↗

bioRxiv2023

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.

biophysics↗

bioRxiv2022

Pump it up: bioelectric stimulation controls tissue hydrostatic pressure and water transport via electro-inflation

Epithelial tissues sheath many organs, separating outside from inside and exquisitely regulating ion and water transport electromechanically to maintain homeostatic balance and tissue hydrostatic pressure. While it is increasingly clear that the ionic microenvironment and external electric stimuli can affect epithelial function and behavior, the coupling between electrical perturbation and tissue form remain unclear. We investigated this by combining electrical stimulation with three-dimensional epithelial tissues with hollow lumens--both kidney cysts and complex intestinal stem cell organoids. Our core finding is that physiological strength electrical stimulation of order 1-3 V/cm (with both direct and alternating currents) can drive powerful and rapid inflation of hollow tissues through a process we call electro-inflation, inducing up to a threefold increase in tissue volume and striking asymmetries in tissue form. Electro-inflation is primarily driven by field-induced ion crowding on the outer surface of the hollow tissue that creates an ion gradient across the epithelial shell, which drives increased ionic flux mediated by ion channels/transporters and subsequent osmotic water flow into the lumen. This influx generates hydrostatic pressure, and inflation results from a competition between this pressure and cell cytoskeletal tension. We validated these interpretations with computational models connecting ion crowding around tissues to tissue mechanics. Electrically stimulated cysts and organoids also exhibited pronounced asymmetry, where the epithelial shell thickened on the cathode-facing side and thinned on the anode-facing side of the tissue. We discovered that this process is the result of 3D electrotaxis-directed migration of cells in an electric field-causing a redistribution of cells around the shell. The ability of electrical cues to dramatically regulate tissue size and shape highlight the key role of the electrical micro-environment and the potential offered by manipulating these signals.

bioengineering↗

bioRxiv2022

Roughening instability of growing 3D bacterial colonies

How do growing bacterial colonies get their shapes? While colony morphogenesis is well-studied in 2D, many bacteria grow as large colonies in 3D environments, such as gels and tissues in the body, or soils, sediments, and subsurface porous media. Here, we describe a morphological instability exhibited by large colonies of bacteria growing in 3D. Using experiments in transparent 3D granular hydrogel matrices, we show that dense colonies of four different species of bacteria--Escherichia coli, Vibrio cholerae, Pseudomonas aeruginosa, and Komagataeibacter sucrofermentans--generically roughen as they consume nutrients and grow beyond a critical size, eventually adopting a characteristic branched, broccoli-like, self-affine morphology independent of variations in the cell type and environmental conditions. This behavior reflects a key difference between 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 rough growth at its surface. We elucidate the onset of roughening 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 growing 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.

biophysics↗

bioRxiv2022

Microbial mutualism generates multistable and oscillatory growth dynamics

Microbial communities typically comprise multiple different species with an intricate network of interactions, ranging from competitive to cooperative, between them. How does the nature of these inter-species interactions impact overall community behavior? While the influence of purely competitive interactions is well-studied, the opposite case of mutualistic interactions--which are also prevalent in many naturally-occurring communities--is poorly understood. Here, we address this gap in knowledge by mathematically modeling a well-mixed two-species community of aerobes and anaerobes having mutualistic metabolic interactions between them. Despite the simplicity of the model, we find that it reproduces three characteristic experimental findings. In particular, in response to changes in the fluxes of exogenously-supplied carbon and oxygen, the community adopts two distinct stable states with differing fractions of aerobes and anaerobes. These states are bistable, capable of arising under identical environmental conditions; transitions between the two are therefore history-dependent and can give rise to oscillations in the bacterial and chemical concentrations. Moreover, using the model, we establish biophysical principles describing how oxygen depletion and nutrient sharing jointly dictate the characteristics of the different states as well as the transitions between them. Altogether, this work thus helps disentangle and highlight the pivotal role of mutualism in governing the overall stability and functioning of microbial communities. Moreover, our model provides a foundation for future studies of more complex communities that play important roles in agriculture, environment, industry, and medicine.

systems biology↗

bioRxiv2021

Membrane fission during bacterial spore development requires DNA-driven cellular inflation

Bacteria require membrane fission for cell division and endospore formation. FisB catalyzes membrane fission during sporulation, but the molecular basis is unclear as it cannot remodel membranes by itself. Sporulation initiates with an asymmetric division that generates a large mother cell and a smaller forespore that contains only 1/4 of its complete 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 membranes undergo fission, the forespore is released into the mother cell cytoplasm. Here we show that forespore inflation and FisB accumulation are both required for efficient membrane fission. We suggest that high membrane tension in the engulfment membrane caused by forespore inflation drives FisB-catalyzed membrane fission. Collectively our data indicate that DNA-translocation has a previously unappreciated second function in energizing FisB-mediated membrane fission under energy-limited conditions. HIGHLIGHTS- Membrane fission during endospore formation requires rapid forespore inflation by ATP-driven DNA translocation. - Forespore inflation is fast enough to increase the tension of the engulfment and forespore membranes to near lysis tensions. - FisB catalyzes membrane fission by impeding the flux of lipids that partially support forespore and engulfment membrane growth. - Membrane fission utilizes chemical energy transduced to mechanical energy during DNA-packing into the forespore.

biophysics↗