arXiv subjects

Ulrich S. Schwarz

Publications and source records attributed to Ulrich S. Schwarz.

At least 19 recordsLinked to original sources

arXiv2026

A viscoelastic theory for ultrasound-induced intracellular streaming

Ultrasound is increasingly used to control biological cells, but its multiple physical effects, including radiation force, streaming, heating, and cavitation, require theoretical frameworks that can quantify their relative strengths. Here we develop a semi-analytical model to predict flow patterns and energy distributions of ultrasound-induced intracellular streaming. Cells are modeled as viscoelastic droplets immersed in a fluid with different viscoelastic properties. For this geometry, the momentum equation with an Oldroyd-B constitutive law is solved using a perturbation expansion commonly applied in acoustofluidics. The resulting equations for the different orders of the expansion are solved using partial wave expansion and explicit integration. We investigate our model for a range of parameters which is relevant both for synthetic polymer and for protein solutions. We find a series of flow reversals that we can connect to the distribution of energy into the different modes. We also consider density and compressibility contrasts, which shift these transitions and introduce new ones. Finally, we discuss the potential biological relevance of our mathematical results for cellular sensing and signaling.

physics.bio-ph↗

arXiv2026

Graph theoretic derivation of mutual linearity for transient probabilities and hitting time distributions in Markov networks

For irreducible, time-homogeneous Markov networks, mutual linearity has recently been established for both occupation probabilities and network currents in the stationary regime as well as in the non-stationary regime in Laplace space. The derivation of this property for the stationary distribution utilized the Markov chain tree theorem, which also allows for an explicit combinatorial expression of the response ratios under variation of a single transition rate. The extension of this result was proven at the trajectory level by employing the Doob Meyer decomposition. By employing the all-minors matrix-tree theorem, we show that this property also follows from a graph theoretic formulation and derive explicit combinatorial expressions for the non-stationary response ratios. The stationary result follows as the long time limit. We also show that the small-time asymptotics are entirely determined by minimal path distances in the underlying graph. Finally we use the graph theoretic approach to prove that mutual linearity also extends to hitting time densities.

cond-mat.stat-mech↗

arXiv2026

Emergence of generic first-passage time distributions for large Markovian networks

First-passage times are often the most relevant aspect of a complex Markovian network because they signify when information processing has resulted in a definite decision. Previous studies have shown that for kinetic proofreading networks in the limit of large network size the first-passage time distribution converges either to a delta or to an exponential distribution. Remarkably, these two forms correspond to the two extreme distributions of minimal and maximal entropy for a fixed mean, respectively. Here we build on the connection between first-passage times and graph theory to show that these two limits are not model-specific, but arise generically in Markovian networks from the distribution of the eigenvalues of the generator matrix. A deterministic peak emerges when infinitely many eigenvalues contribute, while the exponential limit arises from a single dominant eigenvalue. We also show that the exponential limit emerges robustly for reversible networks when the mean first-passage time from the initial state to the target state becomes much larger than the mean first-passage time in the reverse direction. In contrast, the deterministic limit is not obtained from a simple reversal of this condition, but follows from a non-vanishing conductance or a mean-residual lifetime of the process which becomes small compared to the mean first-passage time in the long-time limit. This reveals a fundamental asymmetry between the two regimes. Our theoretical analysis is illustrated and validated by computer simulations of one-step master equations and random networks.

cond-mat.stat-mech↗

arXiv2026

Activation in Vesicle-Mediated Signaling Shaped by Batch Arrival Statistics

Vesicle-mediated secretion of ions or molecules is a central mechanism of cellular communication, for example in processes such as neurotransmission or hormone release. These events are inherently stochastic: vesicle fusions lead to bursts of variable sizes, releasing discrete packets of transmitters that are subsequently cleared or degraded. The dynamics are intrinsically time-directed due to the interplay of spontaneous bursts and continuous degradation. Using generating functions and a recursion relation, we derive an exact solution for the full time-dependent probability distribution of a general batch arrival degradation model. This framework also enables a full analysis of first-passage times to a concentration threshold representing downstream activation. We show that activation kinetics are not determined by mean dynamics alone, but depend sensitively on the temporal statistics of arrival events, batch-size variability, and degradation. In particular, different arrival processes with identical mean rates can lead to qualitatively distinct first passage behavior, reflecting the role of time-asymmetric fluctuations. We also discuss extensions incorporating vesicle depletion. Our results provide a transparent link between stochastic release dynamics and activation timing in vesicle-mediated signaling.

cond-mat.stat-mech↗

arXiv2026

Pathway variability, coat stiffening and mechanical adaptation during clathrin-mediated endocytosis

Clathrin assemblies in cells can persist as flat plaques, abort after partial invagination, or close into clathrin-coated vesicles, but the determinants of these different fates remain unresolved. To investigate the stochastic and complex dynamics of clathrin assemblies, we have developed a kinetic Monte Carlo simulation framework that couples individual clathrin agents to an adaptive continuum membrane. In this hybrid discrete-continuum description, the effective coat bending rigidity and the preferred coat curvature emerge during growth, rather than being prescribed as material parameters. Once connected, curved lattices stiffen from molecular bending modes to coat-level rigidities, because curvature changes require increased stretching or compression, while newly incorporated triskelia hardcode a history-dependent preferred curvature. An analytical theory for non-Euclidean elasticity identifies the relevant internal variables and predicts growth laws that are validated by the simulations. The same microscopic assembly rules yield flat, stalled, and closed coats through two sequential gates in the effective membrane-coat energy landscape. Comparisons with experimentally observed coat geometries and nanodissection-induced curvature changes agree with our theoretical predictions without any fitting parameters. The clathrin coat thus emerges as an adaptive assembly with prestress and memory, whose fate and material parameters reflect the environment in which it has been growing.

q-bio.SC↗

arXiv2026

A theory for coexistence and selection of branched actin networks in a shared and finite pool of monomers

Cellular actin structures are continuously turned over while keeping similar sizes. Since they all compete for a shared pool of actin monomers, the question arises how they can coexist in these dynamic steady states. Recently, the coexistence of branched actin networks with different densities growing in a shared and finite pool of purified proteins has been demonstrated in a biomimetic bead assay. However, theoretical work in the context of organelle size regulation has mainly been focused on linear architectures, such as single filaments and bundles, and thus is not able to explain this observation. Here we show theoretically that the local depletion of actin monomers caused by the growth of a branched network naturally gives rise to a negative feedback loop between network density and growth rate, and that this competition is captured by one central ordinary differential equation. A comprehensive bifurcation analysis shows that the theory leads to well-defined steady states even in the case of multiple networks sharing the same pool of monomers, without any need for specific molecular processes. Under increasing competition strength, coexistence is replaced by selection. We also show that our theory is in excellent agreement with spatiotemporal simulations, implemented in a finite element framework, and that local depletion even occurs in the presence of a large pool of non-polymerizable actin. In summary, our work suggests that local monomer depletion is the decisive and universal factor controlling growth of branched actin networks.

q-bio.SC↗

arXiv2026

Understanding the temperature response of biological systems: Part I -- Phenomenological descriptions and microscopic models

Virtually every biological rate depends on temperature, yet the resulting rate-temperature relationships often deviate strongly from simple Arrhenius behavior. In this first part of a two-part review, we survey phenomenological models used to describe biological temperature responses across scales, from enzymatic reactions to organismal performance. We discuss common functional forms, including symmetric and asymmetric thermal performance curves and extensions of the Arrhenius law, and we highlight how these models define operational quantities such as optimal temperatures, thermal breadths, and thermal limits. We also discuss microscopic models for the effect of temperature, which however do not capture cooperative effects. In Part II of this review, we will discuss how system-level temperature response curves emerge from the interaction of many underlying reactions.

q-bio.QM↗

arXiv2026

Understanding the temperature response of biological systems: Part II -- Network-level mechanisms and emergent dynamics

Building on the phenomenological and microscopic models reviewed in Part I, this second part focuses on network-level mechanisms that generate emergent temperature response curves. We review deterministic models in which temperature modulates the kinetics of coupled biochemical reactions, as well as stochastic frameworks, such as Markov chains, that capture more complex multi-step processes. These approaches show how Arrhenius-like temperature dependence at the level of individual reactions is transformed into non-Arrhenius scaling, thermal limits, and temperature compensation at the system level. Together, network-level models provide a mechanistic bridge between empirical temperature response curves and the molecular organization of biological systems, giving us predictive insights into robustness, perturbations, and evolutionary constraints.

q-bio.MN↗

arXiv2026

Cell bulging and extrusion in a three-dimensional bubbly vertex model for curved epithelial sheets

Cell extrusion is an essential mechanism for controlling cell density in epithelial tissues. Another essential element of epithelia is curvature, which is required to achieve complex shapes, like in the lung or intestine. Here we introduce a three-dimensional bubbly vertex model to study the interplay between extrusion and curvature. We find a generic cellular bulging instability at topological defects which is much stronger than for standard vertex models. Analyzing cell shapes in three-dimensional imaging data of spherical mouse colon organoids, we infer that pentagonal cells have an increased basal interfacial tension, suggesting that cells at topological defects react to the different force conditions. Using the bubbly vertex model, we show that such basal tensions stabilize against the predicted instability and result in better cell shape control than tissue-scale mechanisms such as lumen pressure and spontaneous curvature. Our theory suggests that epithelial curvature naturally leads to bulged and extrusion-like cell shapes because the interfacial curvature of individual cells at the defects strongly amplifies buckling effected by tissue-scale topological defects in elastic sheets. Our results highlight the complex interplay of forces across scales in three-dimensional tissue organization.

physics.bio-ph↗

arXiv2025

The generic temperature response of large biochemical networks

Biological systems are remarkably susceptible to relatively small temperature changes. The most obvious example is fever, when a modest rise in body temperature of only few Kelvin has strong effects on our immune system and how it fights pathogens. Another very important example is climate change, when even smaller temperature changes lead to dramatic shifts in ecosystems. Although it is generally accepted that the main effect of an increase in temperature is the acceleration of biochemical reactions according to the Arrhenius equation, it is not clear how it affects large biochemical networks with complicated architectures. For developmental systems like fly and frog, it has been shown that the system response to temperature deviates in a characteristic manner from the linear Arrhenius plot of single reactions, but a rigorous explanation has not been given yet. Here we use a graph-theoretical interpretation of the mean first-passage times of a biochemical master equation to give a statistical description. We find that in the limit of large system size and if the network has a bias towards a target state, then the Arrhenius plot is generically quadratic, in excellent agreement with numerical simulations for large networks as well as with experimental data for developmental times in fly and frog. We also discuss under which conditions this generic response can be violated, for example for linear chains, which have only one spanning tree.

physics.bio-ph↗

arXiv2025

Three-dimensional chiral active Ornstein-Uhlenbeck model for helical motion of microorganisms

Active movement is essential for the survival of microorganisms like bacteria, algae and unicellular parasites. In three dimensions, both swimming and gliding microorganisms often exhibit helical trajectories. One such case are malaria parasites gliding through 3D hydrogels, for which we find that the internal correlation time for the stochastic process generating propulsion is similar to the time taken for one helical turn. Motivated by this experimental finding, here we theoretically analyze the case of finite internal correlation time for microorganisms with helical trajectories as chiral active particles with an Ornstein-Uhlenbeck process for torque. We present an analytical solution which is in very good agreement with computer simulations. We then show that for this type of internal noise, chirality and rotation increase the persistence of motion and results in helical trajectories that have a larger long-time mean squared displacement than straight trajectories at the same propulsion speed. Finally we provide experimental evidence for this prediction for the case of the malaria parasites.

q-bio.CB↗

arXiv2025

Active gel theory for cell migration with two myosin isoforms

Myosin II molecular motors slide actin filaments relatively to each other and are essential for force generation, motility and mechanosensing in animal cells. For non-muscle cells, evolution has resulted in three different isoforms, which have different properties concerning the motor cycle and also occur in different abundances in the cells, but their respective biological and physical roles are not fully understood. Here we use active gel theory to demonstrate the complementary roles of isoforms A and B for cell migration. We first show that our model can be derived both from coarse-graining kinetic equations and from nonequilibrium thermodynamics as the macroscopic limit of a two-component Tonks gas. We then parametrize the model and show that motile solutions exist, in which the more abundant and more dynamic isoform A is localized to the front and the stronger isoform B to the rear, in agreement with experiments. Exploring parameter space beyond the isoform parameters typical for animal cells, we also find cell oscillations in length and velocity, which might be realized for genetically engineered systems. We also describe an analytical solution for the stiff limit, which then is used to calculate a state diagram, and the effect of actin polymerization at the boundaries, that leads to an imperfect pitchfork bifurcation. Our findings highlight the importance of including isoform-specific molecular details to describe whole cell behavior.

q-bio.CB↗

arXiv2024

The positioning of stress fibers in contractile cells minimizes internal mechanical stress

The mechanics of animal cells is strongly determined by stress fibers, which are contractile filament bundles that form dynamically in response to extracellular cues. Stress fibers allow the cell to adapt its mechanics to environmental conditions and to protect it from structural damage. While the physical description of single stress fibers is well-developed, much less is known about their spatial distribution on the level of whole cells. Here, we combine a finite element method for one-dimensional fibers embedded in an elastic bulk medium with dynamical rules for stress fiber formation based on genetic algorithms. We postulate that their main goal is to achieve minimal mechanical stress in the bulk material with as few fibers as possible. The fiber positions and configurations resulting from this optimization task alone are in good agreement with those found in experiments where cells in 3D-scaffolds were mechanically strained at one attachment point. For optimized configurations, we find that stress fibers typically run through the cell in a diagonal fashion, similar to reinforcement strategies used for composite material.

physics.bio-ph↗

arXiv2024

Coat stiffening can explain invagination of clathrin-coated membranes

Clathrin-mediated endocytosis is the main pathway used by eukaryotic cells to take up extracellular material, but the dominant physical mechanisms driving this process are still elusive. Recently several high-resolution imaging techniques have been used on different cell lines to measure the geometrical properties of clathrin-coated pits over their whole lifetime. Here we first show that the combination of all datasets with the recently introduced cooperative curvature model defines a consensus pathway, which is characterized by a flat to-curved transition at finite area, followed by linear growth and subsequent saturation of curvature. We then apply an energetic model for the composite of plasma membrane and clathrin coat to this consensus pathway to show that the dominant mechanism for invagination could be coat stiffening, which might originate from cooperative interactions between the different clathrin molecules and progressively drives the system towards its intrinsic curvature. Our theory predicts that two length scales determine the invagination pathway, namely the patch size at which the flat-to-curved transition occurs and the final pit radius.

q-bio.SC↗

arXiv2024

Active gel model for one-dimensional cell migration coupling actin flow and adhesion dynamics

Migration of animal cells is based on the interplay between actin polymerization at the front, adhesion along the cell-substrate interface, and actomyosin contractility at the back. Active gel theory has been used before to demonstrate that actomyosin contractility is sufficient for polarization and self-sustained cell migration in the absence of external cues, but did not consider the dynamics of adhesion. Likewise, migration models based on the mechanosensitive dynamics of adhesion receptors usually do not include the global dynamics of intracellular flow. Here we show that both aspects can be combined in a minimal active gel model for one-dimensional cell migration with dynamic adhesion. This model demonstrates that load sharing between the adhesion receptors leads to symmetry breaking, with stronger adhesion at the front, and that bistability of migration arises for intermediate adhesiveness. Local variations in adhesiveness are sufficient to switch between sessile and motile states, in qualitative agreement with experiments.

q-bio.CB↗

arXiv2024

The role of the nucleus for cell mechanics: an elastic phase field approach

The nucleus of eukaryotic cells typically makes up around 30% of the cell volume and has significantly different mechanics, which can make it effectively up to ten times stiffer than the surrounding cytoplasm. Therefore it is an important element for cell mechanics, but a quantitative understanding of its mechanical role during whole cell dynamics is largely missing. Here we demonstrate that elastic phase fields can be used to describe dynamical cell processes in adhesive or confining environments in which the nucleus acts as a stiff inclusion. We first introduce and verify our computational method and then study several applications of large relevance. For cells on adhesive patterns, we find that nuclear stress is shielded by the adhesive pattern. For cell compression between two parallel plates, we obtain force-compression curves that allow us to extract an effective modulus for the cell-nucleus composite. For micropipette aspiration, the effect of the nucleus on the effective modulus is found to be much weaker, highlighting the complicated interplay between extracellular geometry and cell mechanics that is captured by our approach. We also show that our phase field approach can be used to investigate the effects of viscoelasticity and cortical tension.

cond-mat.soft↗

arXiv2024

Morphological instability at topological defects in a three-dimensional vertex model for spherical epithelia

Epithelial monolayers are a central building block of complex organisms. Topological defects have emerged as important elements for single cell behavior in flat epithelia. Here we theoretically study such defects in a three-dimensional vertex model for spherical epithelia like cysts or intestinal organoids. We find that they lead to the same generic morphological instability to an icosahedral shape as it is known from spherical elastic shells like virus capsids, polymerized vesicles or buckyballs. We derive analytical expressions for the effective stretching and bending moduli as a function of the parameters of the vertex model, in excellent agreement with computer simulations. These equations accurately predict both the buckling of a flat epithelial monolayer under uniaxial compression and the faceting transition around the topological defects in spherical epithelia. We further show that localized apico-basal tension asymmetries allow them to reduce the transition threshold to small system sizes.

physics.bio-ph↗

arXiv2022

Optogenetic switching of migration of contractile cells

Cell crawling on flat substrates is based on intracellular flows of the actin cytoskeleton that are driven by both actin polymerization at the front and myosin contractility at the back. The new experimental tool of optogenetics makes it possible to spatially control contraction and thereby possibly also cell migration. Here we analyze this situation theoretically using a one-dimensional active gel model in which the excluded volume interactions of myosin and their aggregation into minifilaments is modeled by a supercritical van der Waals fluid. This physically simple and transparent, but nonlinear and thermodynamically rigorous model predicts bistability between sessile and motile solutions. We then show that one can switch between these two states at realistic parameter ranges via optogenetic activation or inhibition of contractility, in agreement with recent experiments. We also predict the required activation strengths and initiation times.

q-bio.SC↗