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Robert G. Endres

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Published work

26 published item(s)

preprint2026arXiv

How nature discovers rare Turing islands: exploration by common limit cycles

Turing patterns are a cornerstone of biological self-organization, yet their emergence typically requires finely tuned parameters occupying narrow regions of high-dimensional space. This poses a fundamental challenge: how can evolving biological systems reliably find and exploit such rare conditions? In this work, we propose that common biochemical limit cycles, such as those arising from genetic feedback loops, can act as natural explorers of Turing space. By coupling a reaction-diffusion system to an orbit that modulates some of its parameters, we show that the system can dynamically sweep through Turing-permissive regimes and generate transient spatial patterns. We use an entropy-based measure in Fourier space to quantify pattern formation and demonstrate how cycles enhance the detectability and robustness of Turing islands. We further explore how coupling to positional gradients increases reproducibility, suggesting a route from oscillatory dynamics to stable developmental programs. Our results highlight a powerful mechanism by which nature might bootstrap complex spatial structure from simple temporal motifs.

preprint2026arXiv

Is E. coli good at chemotaxis?

Bacteria seem masters of chemotaxis, yet recent work suggests otherwise. Henry Mattingly and colleagues (Nature Physics, 2026) argue that Escherichia coli uses only a small fraction of the sensory information available at its surface, challenging the long-held view that bacterial chemotaxis operates near physical sensing limits. This article offers a brief conceptual discussion of their findings, placing them in the context of classical chemotaxis models, robustness to noise, and broader perspectives drawn from physics, biology, and Greek mythology.

preprint2022arXiv

T cell morphodynamics reveal periodic shape oscillations in 3D migration

T cells use sophisticated shape dynamics (morphodynamics) to migrate towards and neutralise infected and cancerous cells. However, there is limited quantitative understanding of the migration process in 3D extracellular matrices (ECMs) and across timescales. Here, we leveraged recent advances in lattice light-sheet microscopy to quantitatively explore the 3D morphodynamics of migrating T cells at high spatiotemporal resolution. We first developed a new shape descriptor based on spherical harmonics, incorporating key polarisation information of the uropod. We found that the shape space of T cells is low-dimensional. At the behavioural level, run-and-stop migration modes emerge at ~150 s, and we mapped the morphodynamic composition of each mode using multiscale wavelet analysis, finding 'stereotyped' motifs. Focusing on the run mode, we found morphodynamics oscillating periodically (every ~100 s) that can be broken down into a biphasic process: front-widening with retraction of the uropod, followed by a rearward surface motion and forward extension, where intercalation with the ECM in both of these steps likely facilitates forward motion. Further application of these methods may enable the comparison of T cell migration across different conditions (e.g. differentiation, activation, tissues, and drug treatments), and improve the precision of immunotherapeutic development.

preprint2021arXiv

Physics-Informed Deep Learning Characterizes Morphodynamics of Asian Soybean Rust Disease

Medicines and agricultural biocides are often discovered using large phenotypic screens across hundreds of compounds, where visible effects of whole organisms are compared to gauge efficacy and possible modes of action. However, such analysis is often limited to human-defined and static features. Here, we introduce a novel framework that can characterize shape changes (morphodynamics) for cell-drug interactions directly from images, and use it to interpret perturbed development of Phakopsora pachyrhizi, the Asian soybean rust crop pathogen. We describe population development over a 2D space of shapes (morphospace) using two models with condition-dependent parameters: a top-down Fokker-Planck model of diffusive development over Waddington-type landscapes, and a bottom-up model of tip growth. We discover a variety of landscapes, describing phenotype transitions during growth, and identify possible perturbations in the tip growth machinery that cause this variation. This demonstrates a widely-applicable integration of unsupervised learning and biophysical modeling.

preprint2021arXiv

Thermodynamic constraints on the assembly and diversity of microbial ecosystems are different near to and far from equilibrium

Non-equilibrium thermodynamics has long been an area of substantial interest to ecologists because most fundamental biological processes, such as protein synthesis and respiration, are inherently energy-consuming. Microbial communities are a natural system to decipher this mechanistic basis because their interactions in the form of substrate consumption, metabolite production, and cross-feeding can be described explicitly in thermodynamic terms. Previous work has considered how thermodynamic constraints impact competition between pairs of species, but restrained from analysing how this manifests in complex dynamical systems. To address this gap, we develop a thermodynamic microbial community model with fully reversible reaction kinetics, which allows direct consideration of free-energy dissipation. This also allows species to interact via products rather than just substrates, increasing the dynamical complexity, and allowing a more nuanced classification of interaction types to emerge. Using this model, we find that community diversity increases with substrate lability, because greater free-energy availability allows for faster generation of niches. Thus, more niches are generated in the time frame of community establishment, leading to higher final species diversity. We also find that allowing species to make use of near-to-equilibrium reactions increases diversity in a low free-energy regime. In such a regime, two new thermodynamic interaction types that we identify here reach comparable strengths to the conventional (competition and facilitation) types, emphasising the key role that thermodynamics plays in community dynamics. Our results suggest that accounting for realistic thermodynamic constraints is vital for understanding the dynamics of real-world microbial communities.

preprint2020arXiv

Thermodynamics of switching in multistable non-equilibrium systems

Multistable non-equilibrium systems are abundant outcomes of nonlinear dynamics with feedback but still relatively little is known about what determines the stability of the steady states and their switching rates in terms of entropy and entropy production. Here, we will link fluctuation theorems for the entropy production along trajectories with the action obtainable from the Freidlin--Wentzell theorem to elucidate the thermodynamics of switching between states in the large volume limit of multistable systems. We find that the entropy production at steady state plays no role, but the entropy production during switching is key. Steady-state entropy and diffusive noise strength can be neglected in this limit. The relevance to biology, ecological, and climate models is apparent.

preprint2016arXiv

Target shape dependence in a simple model of receptor-mediated endocytosis and phagocytosis

Phagocytosis and receptor-mediated endocytosis are vitally important particle uptake mechanisms in many cell types, ranging from single-cell organisms to immune cells. In both processes, engulfment by the cell depends critically on both particle shape and orientation. However, most previous theoretical work has focused only on spherical particles and hence disregards the wide-ranging particle shapes occurring in nature, such as those of bacteria. Here, by implementing a simple model in one and two dimensions, we compare and contrast receptor-mediated endocytosis and phagocytosis for a range of biologically relevant shapes, including spheres, ellipsoids, capped cylinders, and hourglasses. We find a whole range of different engulfment behaviors with some ellipsoids engulfing faster than spheres, and that phagocytosis is able to engulf a greater range of target shapes than other types of endocytosis. Further, the 2D model can explain why some nonspherical particles engulf fastest (not at all) when presented to the membrane tip-first (lying flat). Our work reveals how some bacteria may avoid being internalized simply because of their shape, and suggests shapes for optimal drug delivery.

preprint2015arXiv

Bacterial chemotaxis: information processing, thermodynamics, and behavior

Escherichia coli has long been used as a model organism due to the extensive experimental characterization of its pathways and molecular components. Take chemotaxis as an example, which allows bacteria to sense and swim in response to chemicals, such as nutrients and toxins. Many of the pathway's remarkable sensing and signaling properties are now concisely summarized in terms of design (or engineering) principles. More recently, new approaches from information theory and stochastic thermodynamics have begun to address how pathways process environmental stimuli and what the limiting factors are. However, to fully capitalize on these theoretical advances, a closer connection with single-cell experiments will be required.

preprint2015arXiv

Know the single-receptor sensing limit? Think again

How cells reliably infer information about their environment is a fundamentally important question. While sensing and signaling generally start with cell-surface receptors, the degree of accuracy with which a cell can measure external ligand concentration with even the simplest device - a single receptor - is surprisingly hard to pin down. Recent studies provide conflicting results for the fundamental physical limits. Comparison is made difficult as different studies either suggest different readout mechanisms of the ligand-receptor occupancy, or differ on how ligand diffusion is implemented. Here we critically analyse these studies and present a unifying perspective on the limits of sensing, with wide-ranging biological implications.

preprint2015arXiv

Protein connectivity in chemotaxis receptor complexes

The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET) measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.

preprint2014arXiv

Bistable forespore engulfment in Bacillus subtilis by a zipper mechanism in absence of the cell wall

To survive starvation, the bacterium Bacillus subtilis forms durable spores. The initial step of sporulation is asymmetric cell division, leading to a large mother-cell and a small forespore compartment. After division is completed and the dividing septum is thinned, the mother cell engulfs the forespore in a slow process based on cell-wall degradation and synthesis. However, recently a new cell-wall independent mechanism was shown to significantly contribute, which can even lead to fast engulfment in $\sim$ 60 $%$ of the cases when the cell wall is completely removed. In this backup mechanism, strong ligand-receptor binding between mother-cell protein SpoIIIAH and forespore-protein SpoIIQ leads to zipper-like engulfment, but quantitative understanding is missing. In our work, we combined fluorescence image analysis and stochastic Langevin simulations of the fluctuating membrane to investigate the origin of fast bistable engulfment in absence of the cell wall. Our cell morphologies compare favorably with experimental time-lapse microscopy, with engulfment sensitive to the number of SpoIIQ-SpoIIIAH bonds in a threshold-like manner. By systematic exploration of model parameters, we predict regions of osmotic pressure and membrane-surface tension that produce successful engulfment. Indeed, decreasing the medium osmolarity in experiments prevents engulfment in line with our predictions. Forespore engulfment may thus not only be an ideal model system to study decision-making in single cells, but its biophysical principles are likely applicable to engulfment in other cell types, e.g. during phagocytosis in eukaryotes.

preprint2014arXiv

Memory improves precision of cell sensing in fluctuating environments

Biological cells are often found to sense their chemical environment near the single-molecule detection limit. Surprisingly, this precision is higher than simple estimates of the fundamental physical limit, hinting towards active sensing strategies. In this work, we analyse the effect of cell memory, e.g. from slow biochemical processes, on the precision of sensing by cell-surface receptors. We derive analytical formulas, which show that memory significantly improves sensing in weakly fluctuating environments. However, surprisingly when memory is adjusted dynamically, the precision is always improved, even in strongly fluctuating environments. In support of this prediction we quantify the directional biases in chemotactic Dictyostelium discoideum cells in a flow chamber with alternating chemical gradients. The strong similarities between cell sensing and control engineering suggest universal problem-solving strategies of living matter.

preprint2014arXiv

Predicting chemical environments of bacteria from receptor signaling

Sensory systems have evolved to respond to input stimuli of certain statistical properties, and to reliably transmit this information through biochemical pathways. Hence, for an experimentally well-characterized sensory system, one ought to be able to extract valuable information about the statistics of the stimuli. Based on dose-response curves from in vivo fluorescence resonance energy transfer (FRET) experiments of the bacterial chemotaxis sensory system, we predict the chemical gradients chemotactic Escherichia coli cells typically encounter in their natural environment. To predict average gradients cells experience, we revaluate the phenomenological Weber's law and its generalizations to the Weber-Fechner law and fold-change detection. To obtain full distributions of gradients we use information theory and simulations, considering limitations of information transmission from both cell-external and internal noise. We identify broad distributions of exponential gradients, which lead to log-normal stimuli and maximal drift velocity. Our results thus provide a first step towards deciphering the chemical nature of complex, experimentally inaccessible cellular microenvironments, such as the human intestine.

preprint2014arXiv

The mechanism of phagocytosis: two stages of engulfment

Despite being of vital importance to the immune system, the mechanism by which cells engulf relatively large solid particles during phagocytosis is still poorly understood. From movies of neutrophil phagocytosis of polystyrene beads, we measure the fractional engulfment as a function of time and demonstrate that phagocytosis occurs in two distinct stages. During the first stage, engulfment is relatively slow and progressively slows down as phagocytosis proceeds. However, at approximately half-engulfment, the rate of engulfment increases dramatically, with complete engulfment attained soon afterwards. By studying simple mathematical models of phagocytosis, we suggest that the first stage is due to a passive mechanism, determined by receptor diffusion and capture, whereas the second stage is more actively controlled, perhaps with receptors being driven towards the site of engulfment. We then consider a more advanced model that includes signaling and captures both stages of engulfment. This model predicts that there is an optimum ligand density for quick engulfment. Further, we show how this model explains why non-spherical particles engulf quickest when presented tip-first. Our findings suggest that active regulation may be a later evolutionary innovation, allowing fast and robust engulfment even for large particles.

preprint2013arXiv

Distinct cell shapes determine accurate chemotaxis

The behaviour of an organism often reflects a strategy for coping with its environment. Such behaviour in higher organisms can often be reduced to a few stereotyped modes of movement due to physiological limitations, but finding such modes in amoeboid cells is more difficult as they lack these constraints. Here, we examine cell shape and movement in starved Dictyostelium amoebae during migration toward a chemoattractant in a microfluidic chamber. We show that the incredible variety in amoeboid shape across a population can be reduced to a few modes of variation. Interestingly, cells use distinct modes depending on the applied chemical gradient, with specific cell shapes associated with shallow, difficult-to-sense gradients. Modelling and drug treatment reveals that these behaviours are intrinsically linked with accurate sensing at the physical limit. Since similar behaviours are observed in a diverse range of cell types, we propose that cell shape and behaviour are conserved traits.

preprint2013arXiv

Dynamics of Natural Killer cell receptor revealed by quantitative analysis of photoswitchable protein

Natural Killer (NK) cell activation is dynamically regulated by numerous activating and inhibitory surface receptors that accumulate at the immune synapse. Quantitative analysis of receptor dynamics has been limited by methodologies which rely on indirect measurements such as fluorescence recovery after photobleaching. Here, we report a novel approach to study how proteins traffic to and from the immune synapse using NK cell receptors tagged with the photoswitchable fluorescent protein tdEosFP, which can be irreversibly photoswitched from a green to red fluorescent state by ultraviolet light. Thus, following a localized switching event, the movement of the photoswitched molecules can be temporally and spatially resolved by monitoring fluorescence in two regions of interest. By comparing images with mathematical models, we evaluated the diffusion coefficient of the receptor KIR2DL1 (0.23 +- 0.06 micron^2/s) and assessed how synapse formation affects receptor dynamics. Our data conclude that the inhibitory NK cell receptor KIR2DL1 is continually trafficked into the synapse and remains surprisingly stable there. Unexpectedly however, in NK cells forming synapses with multiple target cells simultaneously, KIR2DL1 at one synapse can relocate to another synapse. Thus, our results reveal a previously undetected inter-synaptic exchange of protein.

preprint2013arXiv

Unraveling Adaptation in Eukaryotic Pathways: Lessons from Protocells

Eukaryotic adaptation pathways operate within wide-ranging environmental conditions without stimulus saturation. Despite numerous differences in the adaptation mechanisms employed by bacteria and eukaryotes, all require energy consumption. Here, we present two minimal models showing that expenditure of energy by the cell is not essential for adaptation. Both models share important features with large eukaryotic cells: they employ small diffusible molecules and involve receptor subunits resembling highly conserved G-protein cascades. Analyzing the drawbacks of these models helps us understand the benefits of energy consumption, in terms of adjustability of response and adaptation times as well as separation of cell-external sensing and cell-internal signaling. Our work thus sheds new light on the evolution of adaptation mechanisms in complex systems.

preprint2011arXiv

Optimal receptor-cluster size determined by intrinsic and extrinsic noise

Biological cells sense external chemical stimuli in their environment using cell-surface receptors. To increase the sensitivity of sensing, receptors often cluster, most noticeably in bacterial chemotaxis, a paradigm for signaling and sensing in general. While amplification of weak stimuli is useful in absence of noise, its usefulness is less clear in presence of extrinsic input noise and intrinsic signaling noise. Here, exemplified on bacterial chemotaxis, we combine the allosteric Monod-Wyman- Changeux model for signal amplification by receptor complexes with calculations of noise to study their interconnectedness. Importantly, we calculate the signal-to-noise ratio, describing the balance of beneficial and detrimental effects of clustering for the cell. Interestingly, we find that there is no advantage for the cell to build receptor complexes for noisy input stimuli in absence of intrinsic signaling noise. However, with intrinsic noise, an optimal complex size arises in line with estimates of the sizes of chemoreceptor complexes in bacteria and protein aggregates in lipid rafts of eukaryotic cells.

preprint2010arXiv

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.

preprint2010arXiv

Increased accuracy of ligand sensing by receptor diffusion on cell surface

The physical limit with which a cell senses external ligand concentration corresponds to the perfect absorber, where all ligand particles are absorbed and overcounting of same ligand particles does not occur. Here we analyze how the lateral diffusion of receptors on the cell membrane affects the accuracy of sensing ligand concentration. Specifically, we connect our modeling to neurotransmission in neural synapses where the diffusion of glutamate receptors is already known to refresh synaptic connections. We find that receptor diffusion indeed increases the accuracy of sensing for both the glutamate AMPA and NDMA receptors, although the NMDA receptor is overall much noiser. We propose that the difference in accuracy of sensing of the two receptors can be linked to their different roles in neurotransmission. Specifically, the high accuracy in sensing glutamate is essential for the AMPA receptor to start membrane depolarization, while the NMDA receptor is believed to work in a second stage as a coincidence detector, involved in long-term potentiation and memory.

preprint2010arXiv

Increased accuracy of ligand sensing by receptor internalization

Many types of cells can sense external ligand concentrations with cell-surface receptors at extremely high accuracy. Interestingly, ligand-bound receptors are often internalized, a process also known as receptor-mediated endocytosis. While internalization is involved in a vast number of important functions for the life of a cell, it was recently also suggested to increase the accuracy of sensing ligand as the overcounting of the same ligand molecules is reduced. Here we show, by extending simple ligand-receptor models to out-of-equilibrium thermodynamics, that internalization increases the accuracy with which cells can measure ligand concentrations in the external environment. Comparison with experimental rates of real receptors demonstrates that our model has indeed biological significance.

preprint2010arXiv

The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape

Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood. Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcyRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes. This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.

preprint2009arXiv

Accuracy of direct gradient sensing by single cells

Many types of cells are able to accurately sense shallow gradients of chemicals across their diameters, allowing the cells to move towards or away from chemical sources. This chemotactic ability relies on the remarkable capacity of cells to infer gradients from particles randomly arriving at cell-surface receptors by diffusion. Whereas the physical limits of concentration sensing by cells have been explored, there is no theory for the physical limits of gradient sensing. Here, we derive such a theory, using as models a perfectly absorbing sphere and a perfectly monitoring sphere, which, respectively, infer gradients from the absorbed surface particle density or the positions of freely diffusing particles inside a spherical volume. We find that the perfectly absorbing sphere is superior to the perfectly monitoring sphere, both for concentration and gradient sensing, since previously observed particles are never remeasured. The superiority of the absorbing sphere helps explain the presence at the surfaces of cells of signal degrading enzymes, such as PDE for cAMP in Dictyostelium discoideum (Dicty) and BAR1 for mating factor alpha in Saccharomyces cerevisiae (budding yeast). Quantitatively, our theory compares favorably to recent measurements of Dicty moving up a cAMP gradient, suggesting these cells operate near the physical limits of gradient detection.

preprint2009arXiv

Biophysical mechanism for Ras-nanocluster formation and signaling in plasma membrane

Ras GTPases are lipid-anchored G proteins which play a fundamental role in cell signaling processes. Electron micrographs of immunogold-labeled Ras have shown that membrane-bound Ras molecules segregate into nanocluster domains. Several models have been developed in attempts to obtain quantitative descriptions of nanocluster formation, but all have relied on assumptions such as a constant, expression-level independent ratio of Ras in clusters to Ras monomers (cluster/monomer ratio). However, this assumption is inconsistent with the law of mass action. Here, we present a biophysical model of Ras clustering based on short-range attraction and long-range repulsion between Ras molecules in the membrane. To test this model, we performed Monte Carlo simulations and compared statistical clustering properties with experimental data. We find that we can recover the experimentally-observed clustering across a range of Ras expression levels, without assuming a constant cluster/monomer ratio or the existence of lipid rafts. In addition, our model makes predictions about the signaling properties of Ras nanoclusters in support of the idea that Ras nanoclusters act as an analog-digital-analog converter for high fidelity signaling.

preprint2009arXiv

Maximum likelihood and the single receptor

Biological cells are able to accurately sense chemicals with receptors at their surfaces, allowing cells to move towards sources of attractant and away from sources of repellent. The accuracy of sensing chemical concentration is ultimately limited by the random arrival of particles at the receptors by diffusion. This fundamental physical limit is generally considered to be the Berg & Purcell limit [H.C. Berg and E.M. Purcell, Biophys. J. {\bf 20}, 193 (1977)]. Here we derive a lower limit by applying maximum likelihood to the time series of receptor occupancy. The increased accuracy stems from solely considering the unoccupied time intervals - disregarding the occupied time intervals as these do not contain any information about the external particle concentration, and only decrease the accuracy of the concentration estimate. Receptors which minimize the bound time intervals achieve the highest possible accuracy. We discuss how a cell could implement such an optimal sensing strategy by absorbing or degrading bound particles.

preprint2009arXiv

Polar Chemoreceptor Clustering by Coupled Trimers of Dimers

Receptors of bacterial chemotaxis form clusters at the cell poles, where clusters act as "antennas" to amplify small changes in ligand concentration. Interestingly, chemoreceptors cluster at multiple length scales. At the smallest scale, receptors form dimers, which assemble into stable timers of dimers. At a large scale, trimers form large polar clusters composed of thousands of receptors. Although much is known about the signaling properties emerging from receptor clusters, it is unknown how receptors localize at the cell poles and what the cluster-size determining factors are. Here, we present a model of polar receptor clustering based on coupled trimers of dimers, where cluster size is determined as a minimum of the cluster-membrane free energy. This energy has contributions from the cluster-membrane elastic energy, penalizing large clusters due to their high intrinsic curvature, and receptor-receptor coupling favoring large clusters. We find that the reduced cluster-membrane curvature mismatch at the curved cell poles leads to large and robust polar clusters in line with experimental observation, while lateral clusters are efficiently suppressed.