Chemotaxis – from Basic Physics to Biology

In 1670s Antonie van Leuwenhoek was probably the first person to describe microbial behaviour. However, despite a number of detailed investigations, it took until the mid 20th century for science to start to make progress towards understanding both the mechanisms of movement and how these might be controlled by signalling pathways. Two very different aspects of science caused the relatively slow progress. One was technology: we needed advances in microscopy, molecular biology and an understanding of the constraints caused by size and fluid dynamics to start getting to grips with movement and sensing in 3 dimensions. The second was scientific assumptions. It was generally assumed that bacteria would move and respond using similar mechanisms to eukaryotic microbes and then that all bacteria would behave like E. coli. I will discuss the major advances that lead to our current understanding and highlight the dangers of extrapolation.

Flagellar motility enables bacteria to navigate natural habitats with a wide range of mechanical properties, from the ocean to the digestive tract and soil. Species differ in the number, position, and shape of their flagella, but the adaptive value of these flagellar architectures is unclear. Many species traverse multiple types of environments, such as pathogens inside and outside a host. We investigated the hypothesis that flagellar architectures mediate environment-specific benefits in the marine pathogen Vibrio alginolyticus which exhibits physiological adaptation to the mechanical environment. In addition to its single polar flagellum, the bacterium produces lateral flagella in environments that differ mechanically from water. These are known to facilitate surface motility and attachment. We used high-throughput 3D bacterial tracking to quantify chemotactic performance of both flagellar architectures in three archetypes of mechanical environments relevant to the bacterium’s native habitats: water, polymer solutions, and hydrogels. We reveal that lateral flagella impede chemotaxis in water by lowering the swimming speed but improve chemotaxis in both types of complex environments. Statistical trajectory analysis reveals two distinct underlying behavioral mechanisms: In viscous solutions of the polymer PVP K90, lateral flagella increase the swimming speed. In agar hydrogels, lateral flagella improve overall chemotactic performance, despite lowering the swimming speed, by preventing trapping in pores. Our findings (1) show that lateral flagella are multi-purpose tools with a wide range of applications beyond surfaces. They implicate flagellar architecture as a mediator of environment-specific benefits and point to a rich space of bacterial navigation behaviors in complex environments. (1) Grognot et al., PNAS 2023, doi:10.1073/pnas.230187312

Collective cell movement is critical to the emergent properties of many multicellular systems, including microbial self-organization in biofilms, wound healing, and cancer metastasis. However, even the best-studied systems lack a complete picture of how diverse physical and chemical cues act upon individual cells to ensure coordinated multicellular behavior. Myxococcus xanthus is a model bacteria famous for its coordinated multicellular behavior resulting in dynamic pattern formation. For example, when starving, millions of cells coordinate their movement to organize into fruiting bodies – aggregates containing tens of thousands of bacteria. Relating these complex self-organization patterns to the behavior of individual cells is a complex reverse-engineering problem that cannot be solved solely by experimental research. Based on the coarse-grained trajectories of tracked cells, we show that self-organization critically depends on the ability of cells to exhibit biased movement toward aggregates. We tested two possible mechanisms for this biased movement: contact-dependent signaling and chemotaxis. The results demonstrate that only a chemotaxis model with adaptation can reproduce the observed experimental results and lead to the formation of stable aggregates. Furthermore, our model reproduces the experimentally observed patterns of cell alignment around aggregates.

Chemotaxis, allowing cells to sense and migrate towards chemicals, is well studied but fundamental questions remain: What is the fundamental physical limit of chemical detection by cells, and how can cells reach this limit? How does purposeful behaviour emerge? Does sensing occur microscopically at the receptor level or via the whole cell body? In this talk, I will provide an overview of relevant work from my group.

Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally guided by self-generated signaling gradients rather than long-range, pre-patterned cues. However, how heterogeneous mixtures of cells interact and navigate through self-generated gradients remains largely unexplored. Here we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that relative chemotactic sensitivity of cell populations controls their long-time coupling and co-migration dynamics, exhibiting an optimal range that leads to robust colocalized migration. Surprisingly, boundary conditions and interactions with an attractant reservoir substantially influence the migration patterns. We test our theoretical predictions with experiments on co-migration of different immune cell populations. Our findings reveal self-generated chemotaxis as an elegant strategy for multicellular navigation beyond external signaling cues or direct intercellular interactions.

In biology, cells can persistently move across gradients of receptors (haptotaxis). There is debate regarding whether this motion is driven by passive adhesion or arises from functionalities triggered by intracellular signaling. In the first part of this talk, we address this question by considering a synthetic system made of vesicles functionalized by DNA ligands reversibly binding complementary sequences (receptors). Using experiments, theory, and simulations, we identified the system parameters affecting the emerging drifting velocity [1]. We then consider systems in which receptor gradients are generated dynamically by the catalytic activity of certain ligands. In particular, we characterize the emerging motility of particles functionalized with ligands that bind to receptors and ligands that cleave receptors, relevant to the study of Influenza A Virus infection [2]. [1] Chemotactic crawling of multivalent vesicles along ligand-density gradients, H. Sleath, B. M. Mognetti, Y. Elani, L. Di Michele, arXiv:2310.09990 [2] The sliding motility of the bacilliform virions of Influenza A viruses† Check for updates, L. Stevens, S. de Buyl, B. M. Mognetti, Soft Matter 19, 4491 (2023)

Active colloids use a variety of mechanisms to self-propel. They usually involve an exchange of matter or energy with the medium in which they are suspended. Because of the intrinsic non-equilibrium nature of such coupling, the properties and regimes of self-propulsion are richer and more varied than the ones associated to their underlying equilibrium properties. In this presentation I will analyze the implications that the dynamic coupling between colloids and reactants may have in how colloids self-propel and how such dynamical couplings can be used to control and manipulate the individual and collective motion of colloids.

Chemotaxis of Active Brownian Chains: Leveraging Constraints for Advantage. Jens-Uwe Sommer, Hidde Vujik, Holger Merlitz, Pietro Luigi Muzzeddu and Abinav Sharma We investigated the dynamics of active Brownian particles in gradients of activity using both theory and simulations. Traditionally, it was believed that single active particles move down the gradient of activity, akin to passive particles in a temperature gradient, thus requiring some level of information processing for chemotaxis, as seen in living organisms. However, we demonstrated that connecting active particles into larger structures, such as active chains, is sufficient to induce chemotaxis in the stationary state. This behavior arises from the back-storing effect of connectivity, which compels active particles to explore the local environment rather than engage in free random motion. Consequently, stationary chemotaxis is observed even when active particles are connected to a passive cargo. We discuss the mechanism of stationary chemotaxis and present analytic solutions for various scenarios, including active-passive dimers, active chains, and rigid active dimers. Specifically, we can identify an order parameter for chemotaxis that depends solely on the connectivity of the active particles and the persistence of active motion.

Chemotaxis, the directed movement of organisms or cells in response to chemical gradients, is a fundamental process that influences the behavior of active matter in diverse environments. This has attracted wide attention in replicating and controlling artificial chemotaxis in laboratory settings. In this study, we have used a microfluidic system to investigate the chemotactic behavior of active Janus colloids, which can address the limitations of previous approaches by excluding the influence of a flowing medium. By employing the stop-flow technique, we can establish a controlled chemical gradient in a static environment, thereby enabling us to observe and quantify behaviors of active colloids in this gradient without any interference from surrounding flow turbulence. Our findings demonstrate that these active Janus colloids exhibit distinct chemotactic behavior, which is influenced by their driving mechanism and surface properties. This can result in particles displaying either positive or negative chemotaxis, or more complex motion patterns within the chemical gradient. This study not only highlights the advantages of microfluidic techniques in understanding the chemotactic mechanisms of active colloids but also has important implications for understanding the behavior of the behavior of living soft matter in natural environments.

Cells migrate along gradients of substrate stiffness — a process called durotaxis. The physical explanation for durotaxis relies on focal adhesions transmitting the cell’s contractile forces to the substrate. Combining experiments and theory, I will show that confined cells can perform durotaxis despite lacking strong or specific adhesions. We show that the mechanism of this adhesion-independent durotaxis is based on the fact that stiffer substrate offers higher friction. We develop a physical model that predicts that non-adherent cells polarize and migrate towards higher friction — a tactic behavior that we call frictiotaxis. We demonstrate frictiotaxis in experiments by showing that cells migrate up a friction gradient even when stiffness is uniform. These results broaden the potential of durotaxis to guide any cell that contacts a substrate. Our work also reveals a new mode of directed migration based on friction, with implications for immune and cancer cells, which commonly move with non-specific interactions.

To perform chemotaxis, biological cells use one of two fundamental gradient-sensing strategies: spatial comparison of concentrations measured at different positions on their surface, or temporal comparison of concentrations measured at different locations visited along their motion path. It is believed that size and speed dictate which gradient-sensing strategy cells choose, yet a formal proof is pending. We introduce a model of an ideal chemotactic agent with unlimited information processing capabilities that combines spatial and temporal comparison. We account for physical limits of chemo-sensation: molecule counting noise at physiological concentrations, and motility noise inevitable at the micro-scale. The agent continuously updates an egocentric likelihood map of relative target position. An analytic theory for this egotaxis agent allows to decompose information gain into contribution from spatial and temporal comparison [1]. Extensive simulation data collapses onto an empirical power-law that predicts an optimal weighting of information as function of motility and sensing noise, demonstrating how spatial comparison becomes more beneficial for agents that are large, slow and less persistent. Our idealized model assuming unlimited information processing capabilities can serve as a benchmark for the chemotaxis of biological cells, and thus to refine heuristic notions on the evolutionary choice of gradient-sensing strategies. [1] Auconi et al. EPL (2023); https://www.biorxiv.org/content/10.1101/2023.10.14.562229v1

Flagellar swimming allows bacteria to travel long distances. When a mobile bacterium approaches a surface, hydrodynamic interactions cause its trajectory to become circular. However, the bacterium's path is marked by periodic reorientations and pauses resulting from changes in the rotational direction of the flagellar bundle. This directional shift occurs at regular intervals, approximately every second, lasting about 100 milliseconds in the case of the bacterium E. coli. These sporadic reorientations enable bacteria to enhance their effective diffusion near surfaces, facilitating environmental exploration. Bacterial chemotaxis takes advantage of a frequency bias in reorientation, allowing the redistribution of bacterial populations to evade toxic environments and move towards favorable regions. Our research focuses on the impact of known chemorepellent substances, such as Ni2+ cations, on bacterial redistribution. Experimental investigations into bacterial motility under varied chemical conditions in microfluidic channels are carried out using dark-field video microscopy. The chemorepulsive diffusion profile of Ni2+ and other cations generates an asymmetric wave. Notably, individual bacteria exhibit a biased motion aligned with the direction of the wave's propagation. The surface behavior of the wave differs from its bulk counterpart. A minimal model, integrating Ni2+ diffusion and chemotactically enhanced bacterial displacement, successfully replicates the asymmetrical shape of the wave and its average speed. The colonization pattern is marked by collective movement in large groups within the bulk and scattering at the surface.

Understanding the fundamental principles governing bacterial motility and navigation is crucial for comprehending critical phenomena, such as infectious disease transmission and biofilm formation. For swimming bacteria, efficient navigation through complex environments, such as structured soil, poses a significant challenge. In this presentation, we will delve into the intricate correlation between the micro-scale navigation of bacteria and their large-scale movement in diverse and heterogeneous environments. We combine experiments, using the soil bacterium *Pseudomonas putida* as a model organism, and active particle modeling. Specifically, we examine how the disordered environment (agar) guides the migration patterns of these bacteria, leading to remarkable motility characteristics. Our research reveals transient subdiffusion of bacteria in agar, primarily due to intermittent trapping. These findings highlight a dynamic hop-and-trap mechanism, with trap times following a power-law distribution. In contrast to the well-studied case of bacterial chemotaxis in uniform bulk fluid, relying mainly on the modulation of run times in dependence of the direction of motion, we provide evidence that the soil bacterium *Pseudomonas putida* also performs chemotaxis in a porous medium where the free path length is severely restricted. The importance of the run time bias as a chemotaxis mechanism decreases for higher agar concentrations. However, we identified a second chemotaxis strategy: the change in direction of motion of bacteria is adjusted after a run, so that the next run phase leads in the direction of the chemotactic gradient (tumble bias).

In this work, we study the emergent dynamics of multicellular aggregates of Dictystelium discoideum undergoing chemotaxis, using an Agent-based modelling approach. In experiments performed by our collaborators, it has been observed that the self-organization of these aggregates resembles active fluids as the population exhibits surface tension, viscosity and bulk diffusion, as it migrates in response to a self-generated chemical gradient. The aim of the present research is to identify and quantify how individual cellular behaviour can give rise to these emergent properties at the population scale.

Approximate Bayesian computation (ABC) has gained considerable interest in recent years as it allows for approximate inference for models with intractable or expensive to calculate likelihoods. ABC replaces the likelihood computation by simulating from the underlying generative model and using the parameters corresponding to the generated observations which are ``close enough'' to the true data to approximate the posterior distribution. Due to the abundance of existing ABC methods, selecting the best one for a given problem can be a challenging task. In this talk we present some results of the use of an ABC algorithm to perform parameter estimation for a complex model of collective cell migration. We consider a hybrid discrete-continuum model for the migration of a population of cells which interact with a background chemical chemoattractant field. Each individual cell acts a moving sink term reflecting the degradation of the chemoattractant through the action of membrane bound enzymes. We perform a sensitivity analysis of the model using a Morris screening approach to give an idea about which parameters in the model are identifiable. We show that the time scale over which measurements are made is key to the reliability of ABC approach for parameter inference. Our results suggest that regardless of the algorithm used, the ABC-posterior distributions depend crucially on the value of the measurement time interval $T$ and that capturing the true parameter uncertainty of the SDE model parameters might be a challenging task for ABC.

The self-propelled, synthetic active matter that transduces chemical energy into mechanical motion are examples of non-equilibrium systems with diverse applications in nanomachinery, fluidics, sensing, and transport. In this context, enzyme-powered propulsion is a classic model where the catalytic reaction has been utilized either by encapsulating enzymes within nanocarriers or tethering them to the vehicle chassis.1,2 In a recent study, we have shown phospholipid vesicles, when tagged with different enzymes, displayed motile behaviour and chemotaxis owing to catalytic conversion of the corresponding substrate solution.3,4 Interestingly, from these results, it was concluded that liposomes when engineered optimally with surface-bound cues could adapt and reconfigure their directional motion in response to interactions with bulk solute molecules. Although liposomes-based drug delivery has gained considerable attention owing to their success in recent RNA-based vaccines, but they need to be rationally designed to evade the formation of ‘protein corona’ to effectively protect cargoes from degradation and deliver them in a targeted and specific way.5 In this context, polymeric nanostructures such as vesicles and micelles comprising of amphiphilic copolymers have been a topic of burgeoning research interest due to their strong repulsive steric potential that can prevent protein fouling and other nonspecific interactions.6 Extensive studies from our group have successfully proved that such polymeric vesicles do not adsorb when incubated with different serum proteins and are highly stable in complex physiological environments. Combining the intriguing results from our lipid and polymer vesicle-based studies, in the ongoing work we aimed to prepare lipid-polymer hybrid vesicles having multifaceted versatility; biocompatibility coming from the lipid segment and chemical robustness from the polymer fraction. By rationally engineering the surface with active cues, we are trying to achieve directional motility and selectivity of the hybrid protocells, and use them as targeted delivery platforms. We anticipate our results to constitute the first steps in fabricating multifunctional motors for carrying out specific functions under physiological conditions. References 1. A. Joseph, G. Battaglia et al. Sci. Adv. 2017, 3, e1700362. 2. S. Ghosh et al. Ann. Rev. Conden. Matter Phys. 2021, 12, 177. 3. S. Ghosh et al. Nano Lett. 2019, 19, 6019. 4. A. Somasundar, S. Ghosh et al. Nature Nanotech. 2019, 14, 1129. 5. S. Wilhelm et al. Nat. Rev. Mater. 2016, 1, 16014. 6. X. Tian et al. Sci. Adv. 2020, 6, eaat0919.

Cell locomotion is essential for early development, the immune response, and wound healing in multicellular organisms, and plays a very deleterious role in cancer metastasis in humans. Locomotion involves the detection and transduction of extracellular chemical and mechanical signals,integration of the signals into an intracellular signal,and the spatio-temporal control of the intracellular biochemical and mechanical responses that lead to force generation, morphological changes and directed movement. We will discuss some of the mathematical and computational challenges that the integration of these processes poses and describe recent progress on some component processes.

Lebewesen im Ozean vom Bakterium bis zum Hai nutzen eine Vielzahl unterschiedlicher Geruchsmoleküle zur Koordination des täglichen Zusammenlebens. Futter, potenzielle Partner, eventuelle Konkurrenten, gefährliche Räuber oder der eigene Nachwuchs werden zumeist "erschnüffelt". Doch diese chemische Sprache des Zusammenlebens ist durch Umweltveränderungen im Kontext des Klimawandels beeinflusst. Dieser Vortrag begleitet Krabben auf der Suche nach ihrem Mittagssnack und beim Eier hüten, zeigt wie Verteidigung und Liebesgeschichten bei Kugelfischen eng verknüpft sind, und taucht in das WG-Leben von Biofilmen aus Mikroalgen und Bakterien ein – immer mit Blick auf das sich ändernde chemische Zusammenspiel im wärmeren und saureren Ozean der Zukunft.

When cells of the social amoeba Dictyostelium discoideum are starved of nutrients they start to synthesize and secrete the chemical messenger and chemoattractant cyclic Adenosine Mono Phosphate (cAMP). This signal is relayed by other cells, resulting in the establishment of periodic waves and cell aggregation. We investigated the chemotactic response of individual cells to repeated exposure to one-dimensional waves of cAMP generated by a microfluidic device. For fast-moving waves (short period), the chemotactic ability of the cells was found to increase upon exposure to more waves, suggesting the development of memory over several cycles. This effect was not significant for slow-moving waves (large period). We showed that the experimental results are consistent with a model that includes a component that rises and decays slowly that is activated by the temporal gradient of cAMP concentration. The observed enhancement in chemotaxis is relevant to populations in the wild: once sustained, periodic waves of the chemoattractant are established, it is beneficial to cells to improve their chemotactic ability to reach the aggregation center sooner. If time permits, some preliminary experimental results on wave propagation and aggregate clustering will be shown.

Groups of cells of all kinds work together as part of multicellular behaviors ranging from collective migration to development. These behaviors are coordinated at the level of single cells, where information about other cells and the environment are encoded in intracellular signaling dynamics that then drive cellular-level behaviors. We face two challenges in understanding how these complex behaviors are coordinated. First, linking these signals and cellular-level behaviors to observed population-wide behaviors is challenging because it requires bridging size- and time-scales. Second, because behaviors are coordinated via information cells can sense locally and this information is shaped by their environments, it is important to interrogate these behaviors in their natural contexts. To address these challenges, we focus on a cellular slime mold, Dictyostelium discoideum, that uses a biochemical environmental signal during starvation to coordinate aggregation into multicellular groups for continued survival. To better understand the signaling dynamics required for coordinating behavior, we take a joint theory-experiment approach where we interrogate mathematical models of how these biochemical signaling dynamics could potentially drive coordinated behaviors with experimental data. Our work suggests several key features of signaling networks are important to robustly coordinate collective multicellular behaviors. To identify how natural environments shape coordination and thus behaviors, we have designed a naturalistic soil model environment where we can visualize how environments interact with different types of cells to affect collective outcomes. Our current findings suggest that the single-cell and population-wide signaling behaviors that coordinate development are robust in highly complex, three-dimensional environments, and that there are also other important cellular properties we do not yet fully understand required for success in nature.

The interplay between cellular growth and cell-cell signaling is essential for the aggregation and proliferation of bacterial colonies, as well as for the self-organization of cell tissues. To investigate this interplay, we focus here on the collective properties of dividing chemotactic cell assemblies by studying their long-time and large-scale dynamics through a renormalization group approach. Our analysis reveals that a novel effective chemotactic interaction -- corresponding to a polarity-induced mechanism -- is generated by fluctuations at macroscopic scales. This term, usually overlooked in phenomenological approaches, emerges from the interplay of the well-known Keller-Segel chemotactic nonlinearity and cell birth and death processes. Its consequences on the critical dynamics will be discussed.

Biological tissues, sediments, and engineered systems are intricate spatially structured mediums characterized by tortuous and porous architectures facilitating fluid flow. The complexity of these environments profoundly influences the colonization patterns of bacteria, modulating factors such as individual cell transport, resource availability, and chemical signaling for communication. However, due to the multi-scale nature of these systems, understanding how various biotic and abiotic properties synergize to regulate bacterial biomass accumulation presents a significant challenge. In this study, we investigate the role of flow-mediated interactions in enabling the gut commensal Escherichia coli to colonize a porous structure resembling the structured surface of mammalian intestines. This structure comprises heterogeneous dead-end pores (DEPs) and connecting percolating channels, or transmitting pores (TPs). Our findings reveal that under flow conditions, gradients of the quorum sensing (QS) signaling molecule autoinducer-2 (AI-2) promote chemotactic accumulation of E. coli in the DEPs. Within these confined spaces, bacterial growth and cell-to-cell collisions facilitate the formation of suspended bacterial aggregates, leading to localized hotspots of resource consumption. Furthermore, when resources become limited, the combined effects of growth and collision dynamics prompt the mechanical evasion of biomass from nutrient and oxygen-depleted DEPs. This intricate interplay between microscale medium structure, complex flow patterns, bacterial quorum sensing, and chemotaxis ultimately governs the heterogeneous accumulation of bacterial biomass in spatially structured environments, such as the villi and crypts of the gut or tortuous pores within soil and filters.

The chemosensory pathway of E. coli is probably the best understood chemosensory in biology. However, it is also one of the simplest with transmembrane trimers of chemoreceptor dimers signalling via a cytoplasmic bound histidine kinase to a mobile response regulator, which, when phosphorylated, diffuses to the switch complex of the motor. Termination of the signal combined with adaptation of the receptors allows the system to reset. The aggregation of the chemoreceptors into large rafts also enables the system to not only respond to small percentage changes in the external concentration of effector, it also allows this to happen over orders of magnitude of background concentration. However, the number of effectors controlling E. coli behaviour is very limited, with only 5 identified, and related, receptors. Other species have over 50 different receptors, with different structures, many cytoplasmic probably sensing metabolic state and allowing more complex ‘decision making’. Chemosensory signals often need to balance with light or oxygen gradients. I will discuss complex sensory pathways in bacteria and how the signals from different pathways may interact to produce a balanced response.

In the complex world of biological systems, we're investigating how molecules move in environments with varying concentrations of charged and neutral solutes. While we know a lot about how charged molecules affect fluid flow near solid surfaces, the behaviour of neutral molecules like glucose is less understood. Glucose, essential for energy, often creates gradients in different parts of the body. We've found that the speed of fluid flow due to glucose gradients is only slightly affected by concentration. Models considering strong interactions, concentration-dependent viscosity, and surface differences help explain this. Understanding these flows is crucial for improving how targeted nanomedicines are delivered. This understanding is also key for developing tiny, self-propelling particles called nano- or microswimmers. By understanding how they move, we can engineer them to navigate tissues and organs, following natural chemical gradients. We've created an entirely synthetic, organic system at the nanoscale that moves towards higher concentrations of glucose. By enclosing glucose oxidase or a combination of glucose oxidase and catalase in biocompatible polymer vesicles, we've shown they can move in response to glucose gradients, which could be useful for targeted drug delivery, especially to the brain. Finally, we've explored the basics of chemotaxis using a simple model mimicking cell components. By encapsulating enzymes and transmembrane proteins in liposomes, we've shown they can move towards areas of higher substrate concentration. This sheds light on how cells respond to chemical signals.

Changsong WU, Xavier BENOIT GONIN, Thierry DARNIGE, Eric CLEMENT, PMMH, CNRS, ESPCI Paris, Sorbonne Université, F-75005, Paris, France\\ Carine DOUARCHE, FAST, CNRS University Paris-Saclay, Orsay, France\\ Rodrigo SOTO3, Department of Physics, University of Chili, Santiago, Chile\\ MSR-1 (magnetospirillum gryphiswaldense) are magnetotactic bacteria that can be grown in the lab. They display two essential features present in the wild: micro-aerotaxis and magnetotaxis, both properties intimately related to the MSR-1 ecological niche taking place at low O2 concentration. This condition is optimal for the synthesis of the magnetosomes responsible for a biased motility in the presence of a magnetic field. The interplay between microaerotaxis and magnetotaxis remains a subtle issue that needs to be fully modeled. To clarify this question, we built a microfluidic chip where the environment in terms of oxygen level, oxygen gradients and magnetic field can be fully controlled around the niche concentration. This device allows to study the collective organization of MSR-1 populations in various conditions and particular the spatio-temporal organization around the niche. We find increasing the O2 concentration at the wall, the passage from (i) wall accumulation, (ii) band splitting and (ii) central band formation which becomes spatially unstable at higher O2 concentration. Moreover, the position of the different structures can be shifted by imposing a mean O2 gradient. In parallel, we designed and solved a simple theoretical model suited to reproduce the aerotactic responses switch around the niche level (low O2 concentration). We present a direct comparisons between the theoretical model and the experiments. Quantitative agreement between the model and the experiments allows to extract the characteristic features of the MSR1 aerotactic response and the oxygen consumption.

The cellular environment, characterized by its intricate composition and spatial organization, hosts a variety of organelles, ranging from membrane-bound ones to membraneless structures that are formed through liquid-liquid phase separation. Cells show precise control over the position of such condensates. We demonstrate that organelle movement in external concentration gradients, diffusiophoresis, is distinct from the one of colloids because fluxes can remain finite inside the liquid-phase droplets and movement of the latter arises from incompressibility. Within cellular domains diffusiophoresis naturally arises from biochemical reactions that are driven by a chemical fuel and produce waste. Simulations and analytical arguments within a minimal model of reaction-driven phase separation reveal that the directed movement stems from two contributions: Fuel and waste are refilled or extracted locally, resulting in concentration gradients, which (i) induce product fluxes via incompressibility and (ii) result in an asymmetric forward reaction in the droplet's surroundings (as well as asymmetric backward reaction inside the droplet), thereby shifting the droplet's position. We show that the former contribution dominates and sets the direction of the movement, away from or towards fuel source and waste sink, depending on the product molecules' affinity towards fuel and waste, respectively. The mechanism thus provides a simple means to organize condensates with different composition. Particle-based simulations and systems with more complex reaction cycles corroborate the robustness and universality of this mechanism.

Cells live in communities where they interact with each other and their environment. By coordinating individuals, such interactions often result in collective behavior that emerge on scales larger than the individuals that are beneficial to the population. At the same time, populations of individuals, even isogenic ones, display phenotypic heterogeneity, which diversifies individual behavior and enhances the resilience of the population in unexpected situations. This raises a dilemma: although individuality provides advantages, it also tends to reduce coordination. I will report on our experimental and theoretical efforts that use bacterial chemotaxis as a model system to understand how populations of cells reconciliate individuality with group behavior and how that leads to adaptation of phenotypic diversity without the need for specific environment-dependent gene regulation or mutations.

Cytokinesis, the final phase of cell division following mitosis, is the process by which two daughter cells are formed and separated. In animal cells, this involves a significant reorganization of the actin cortex, culminating in the creation of a contractile ring and a cleavage furrow within the cell's equatorial zone. This process is characterized by the movement of actin filaments from the cell's poles towards its equator, a phenomenon known as cortical flow. Our theoretical model is designed to explore the dynamics of actin-myosin (AM) filament streaming within the cell during frictiotaxis, a form of cell movement. Unlike the traditional method of durotaxis, which relies on stiffness gradients, frictiotaxis depends on variations in surface friction that may arise from existing physico-chemical irregularities on the contact surface. This approach provides novel insights into how AM filaments accumulate within a cell and the potential sites for AM ring formation during cytokinesis. Consequently, our model offers predictive understanding of the cytokinesis process in cells undergoing frictiotaxis, highlighting the role of friction gradients in directing cell movement and division.

Cancer is one of the most common causes of death worldwide. In 2018, the new cases and deaths were reported to be 18 and 9.6 million persons, respectively. By 2030, it is expected that there will be nearly 17 million deaths. These statistics emphasize the urgency of finding novel and more effective treatments. Bacteria‐assisted tumor‐targeted therapy used as drug-, therapeutic- or gene delivery vehicles has great promise in the treatment of cancer, being versatile for genetic modification for their different uses. During the last years, there have been many advances in bacteriotherapy. Nevertheless, there exist still an interplay of non-linear properties, such as hydrodynamic effects vs bacteria physical and mechanical properties as shape and motility in the swimming bacteria behavior that are far from trivial and largely unexplored, key aspects that must be understood for effective delivery of bacteria inside our body. In this work, I have explored the effects of motility in the bacteria swimming behavior by using the non-motile bacteria E.Coli MG1655 mutant in motAB and modified it genetically to express motAB induced by arabinose in the media to recover its motility. I will present how the bacteria have effectively tuned the motility by using different arabinose concentrations characterizing the swimming behavior in a medium at rest and how the bacteria motility affects its diffusive behavior when swimming in a red blood cell suspension under different flows by using microfluidic chips. I will conclude and present our perspectives and next steps.

My research group focuses on the development of artificial constructs that simulate the structure and functionality of biological cells, using a combination of synthetic and hybrid molecular frameworks engineered for precise manipulation. By mimicking the fundamental characteristics and behaviours of living cells, these cell-like systems offer insights into biological systems, paving the way for a variety of functional applications. A notable challenge in the field of bottom-up synthetic biology is the creation of these synthetic entities capable of dynamic behaviours, such as fusion, material uptake, and autonomous, directional movement in response to environmental stimuli, reflecting the intricate processes of biological communication and organization. The endeavour to construct life-like systems that are both manipulable and interpretable advances our comprehension of life's origins and drive scientific discovery. The fabrication of custom-designed, dynamic cell-like systems holds potential for extensive application in clinical and industrial settings. This rapidly advancing field promises to revolutionize the landscape with the introduction of artificial-cell devices powered by biological compounds. These artificial cell systems are poised to make significant contributions, from aiding in bioremediation efforts to facilitating the creation of biomimetic tissues and materials with controlled spatiotemporal self-organization, showcasing the potential for applications in both environmental and biomedical engineering.

Chemotaxis, the movement of cells guided by chemical gradients, plays an essential role in many biological processes, including tumour dissemination, wound healing, and embryogenesis. Bacteria travel towards or away from a chemical during chemotaxis in search of food and to ensure their survival while the chemical concentration in the immediate surroundings continually changes (temporal). We are focused on understanding the chemotactic movement of eukaryotes and prokaryotes in a controlled chemical environment using microfluidics. We used Dictyostelium discoideum (eukaryotic cells) and Bacteria like Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa as model organisms. Cells of the social amoeba Dictyostelium discoideum migrate to a source of periodic travelling waves of chemoattractant as part of a self-organised aggregation process. Using a novel microfluidic device, we try to understand the aggregation process of Dicty. Also, we are working on rapidly detecting the antibiotic susceptibility of bacteria using a Lab-on-a-chip design. Antibiotic resistance is a growing concern across the world. Because of the increasing usage of antibiotics, these bacteria are becoming resistant to them. Rapid Antibiotic Susceptibility Tests can tell us whether the bacteria are resistant to the particular antibiotic, and we can wisely administer the drug. We try to understand the interplay mechanism between the chemotaxis and antibiotic resistance pathway using novel microfluidics and develop a rapid lab-on-a-chip device capable of detecting antibiotic susceptibility of bacteria based on the understanding.

Intelligent micromotors that directly seek their targets are very useful in practical applications where external control becomes difficult. Although there are many examples of phototactic or chemotactic micromotors in the literature, there is still a need for new strategies that enable effective taxis in small gradients. Natural microorganisms such as light-responsive algae and nutrient-responsive E. coli taxis in extremely small gradients by coordinated rotation and translation. Inspired by them, we propose and verify through Brownian dynamic simulations a strategy for taxis in which the curvature of a microrotor's trajectory changes upon a change in the environmental stimulus. As a result, the microrotor taxis towards regions of small trajectory curvatures by a net accumulation of its displacement over many orbits. This strategy of taxis by varying trajectory curvature is experimentally confirmed by a rod-shaped microrotor moving in circles under light and in a chemical fuel.

A multicomponent mixture of Janus colloids with distinct catalytic coats and phoretic mobilities is a promising theoretical system to explore the collective behavior arising from nonreciprocal interactions. An active colloid produces (or consumes) chemicals, self-propels, drifts along chemical gradients, and rotates its intrinsic polarity to align with a gradient via chemotaxis. As a result the connection from microscopics to continuum theories through coarse-graining couples densities and polarization fields in unique ways. Focusing on a binary mixture, we show that these couplings render the unpatterned reference state unstable to small perturbations through a variety of instabilities including oscillatory ones which arise on crossing an exceptional point or through a Hopf bifurcation. For fast relaxation of the polar fields, they can be eliminated in favor of the density fields to obtain a microscopic realization of the Nonreciprocal Cahn-Hilliard model for two conserved species with two distinct sources of non-reciprocity, one in the interaction coefficient and the other in the interfacial tension. Our work establishes Janus colloids as a versatile model for a bottom-up approach to both scalar and polar active mixtures.

Mathematical models for chemotaxis date back more than half a century and form part of the bedrock of mathematical and computational biology. A point of particular interest has been their capacity to describe instances of macroscopic self-organisation, a feature that has led to their adoption in phenomena that range from microbiology to ecological systems. Here I will briefly review some of the developments in this field, in particular focusing on the connection between microscopic and macroscopic models. I will then consider more recent applications of these models to explain hair follicle and feather bud morphogenesis during embryonic development, integrating models with experimental datasets.

Morphogenesis involves the transformation of initially simple shapes, such as multicellular spheroids, into more complex 3D shapes. These shape changes are governed by mechanical forces including molecular motor-generated forces as well as hydrostatic fluid pressure, both of which are actively regulated in living matter through mechano-chemical feedback. Inspired by autonomous, biophysical shape change, such as occurring in the model organism hydra, we introduce a minimal, active, elastic model featuring a network of springs in a globe-like spherical shell geometry. In this model there is coupling between activity and the shape of the shell: if the local curvature of a filament represented by a spring falls below a critical value, its elastic constant is actively changed. This results in deformation of the springs that changes the shape of the shell. By combining excitation of springs and pressure regulation, we show that the shell undergoes a transition from spheroidal to either elongated ellipsoidal or a different spheroidal shape, depending on pressure. There exists a critical pressure at which there is an abrupt change from ellipsoids to spheroids, showing that pressure is potentially a sensitive switch for material shape. More complex shapes, involving loss of cylindrical symmetry, can arise when springs are excited both above (spring constants increase) and below (spring constants decrease) the curvature threshold. We thus offer biologically inspired design principles for autonomous shape transitions in active elastic shells.

We characterize the full spatiotemporal gait of populations of swimming Escherichia coli using renewal processes to analyze the measurements of intermediate scattering functions [1,2]. This allows us to demonstrate quantitatively how the persistence length of an engineered strain can be controlled by a chemical inducer and to report a controlled transition from perpetual tumbling to smooth swimming. For wild-type E. coli, we measure simultaneously the microscopic motility parameters and the large-scale effective diffusivity, hence quantitatively bridging for the first time small-scale directed swimming and macroscopic diffusion. Moreover, we extend our theory to analytically study a minimal model of a chemotactic agent and provide a spatiotemporal characterization of the underlying dynamics. [1] C Kurzthaler, Y Zhao et al. Phys. Rev. Lett. 132 (2024) [2] Y Zhao, C Kurzthaler et al. Phys. Rev. E 109 (2024)