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Benjamin M. Friedrich

Publications and source records attributed to Benjamin M. Friedrich.

At least 19 recordsLinked to original sources

Motor shot noise explains active fluctuations in a single cilium

Mesoscopic fluctuations reveal stochastic dynamics of molecules in both inanimate and living matter. We investigate how small-number fluctuations shape the collective dynamics of molecular motors using motile cilia as model system. We theoretically show that fluctuations in the number of bound motors are sufficient to explain experimentally observed fluctuations in the cilia beat, including a quality factor $Q$ that measures oscillation precision and phase defects of intra-cilium synchronization. Our findings constrain theories of motor control and establish a link between microscopic motor noise and mesoscopic non-equilibrium dynamics.

physics.bio-ph

Learning stochastic filtering

We quantify the performance of approximations to stochastic filtering by the Kullback-Leibler divergence to the optimal Bayesian filter. Using a two-state Markov process that drives a Brownian measurement process as prototypical test case, we compare two stochastic filtering approximations: a static low-pass filter as baseline, and machine learning of Voltera expansions using nonlinear Vector Auto Regression (nVAR). We highlight the crucial role of the chosen performance metric, and present two solutions to the specific challenge of predicting a likelihood bounded between $0$ and $1$.

cond-mat.stat-mech

Synchronization in cilia carpets and the Kuramoto model with local coupling: breakup of global synchronization in the presence of noise

Carpets of beating cilia represent a paradigmatic example of self-organized synchronization of noisy biological oscillators, characterized by traveling waves of cilia phase. We present a multi-scale model of a cilia carpet, which comprises realistic hydrodynamic interactions between cilia computed for a chiral cilia beat pattern from unicellular Paramecium and active noise of the cilia beat. We demonstrate an abrupt loss of global synchronization beyond a characteristic noise strength. We characterize stochastic transitions between synchronized and disordered dynamics, which generalizes the notion of phase slips in pairs of coupled noisy phase oscillators. Our theoretical work establishes a link between the two-dimensional Kuramoto model of phase oscillators with mirror-symmetric oscillator coupling and detailed models of biological oscillators with asymmetric, chiral interactions.

physics.bio-ph

Research Notes: Gradient sensing in Bayesian chemotaxis

Bayesian chemotaxis is an information-based target search problem inspired by biological chemotaxis. It is defined by a decision strategy coupled to the dynamic estimation of target position from detections of signaling molecules. We extend the case of a point-like agent previously introduced in [Vergassola et al., Nature 2007], which establishes concentration sensing as the dominant contribution to information processing, to the case of a circular agent of small finite size. We identify gradient sensing and a Laplacian correction to concentration sensing as the two leading-order expansion terms in the expected entropy variation. Numerically, we find that the impact of gradient sensing is most relevant because it provides direct directional information to break symmetry in likelihood distributions, which are generally circle-shaped by concentration sensing.

physics.bio-ph

Synchronization in cilia carpets: multiple metachronal waves are stable, but one wave dominates

Carpets of actively bending cilia represent arrays of biological oscillators that can exhibit self-organized metachronal synchronization in the form of traveling waves of cilia phase. This metachronal coordination supposedly enhances fluid transport by cilia carpets. Using a multi-scale model calibrated by an experimental cilia beat pattern, we predict multi-stability of wave modes. Yet, a single mode, corresponding to a dexioplectic wave, has predominant basin-of-attraction. Similar to a "dynamic" Mermin-Wagner theorem, relaxation times diverge with system size, which rules out global order in infinite systems. In finite systems, we characterize the synchronization transition as function of quenched frequency disorder, using generalized Kuramoto order parameters. Our framework termed Lagrangian Mechanics of Active Systems allows to predict the direction and stability of metachronal synchronization for given beat patterns.

physics.bio-ph

Surfing along concentration filaments: sperm chemotaxis in physiological shear flows

Many motile biological cells navigate along concentration gradients of signaling molecules: This chemotaxis guides for instance sperm cells from marine invertebrates, which have to find egg cells in the ocean. While chemotaxis has been intensively studied for idealized conditions of rotationally symmetric gradients in still water, natural gradients are usually distorted, e.g., by turbulent flows in the ocean. Recent experiments and direct numerical simulations with sperm cells and bacteria surprisingly suggest the existence of an optimal flow strength at which chemotaxis is more effective than for still water. We use sperm chemotaxis in simple shear flow as a prototypical example to understand the origin of such an optimal flow strength theoretically: We quantify how flow accelerates spreading of signaling molecules released by the egg, but distorts the resulting concentration field into long and thin filaments. The competition between these two effects sets an optimal flow strength that maximizes sperm-egg encounter. We characterize how sperm cells `surf' along concentration filaments, typical for scalar turbulence, revealing a general navigation paradigm in the presence of flow. We compare both simulation and theory with previous experimental results and find good agreement.

physics.bio-ph

Composite search of active particles in three-dimensional space based on non-directional cues

We theoretically address minimal search strategies of active, self-propelled particles towards hidden targets in three-dimensional space. The particles can sense if a target is close, e.g., by detecting signaling molecules released by a target, but they cannot deduce any directional cues. We focus on composite search strategies, where particles switch between extensive outer search and intensive inner search; inner search is started when the proximity of a target is detected and ends again when a certain inner search time has elapsed. In the simplest strategy, active particles move ballistically during outer search, and transiently reduce their directional persistence during inner search. In a second, adaptive strategy, particles exploit a dynamic scattering effect by reducing directional persistence only outside a well-defined target zone. These two search strategies require only minimal information processing capabilities and a single binary or tertiary internal state, respectively, yet increases the rate of target encounter substantially. The optimal inner search time scales as a power-law with exponent -2/3 with target density, reflecting a trade-off between exploration and exploitation.

cond-mat.soft

Fluctuation-response theorem for Kullback-Leibler divergences to quantify causation

We define a new measure of causation from a fluctuation-response theorem for Kullback-Leibler divergences, based on the information-theoretic cost of perturbations. This information response has both the invariance properties required for an information-theoretic measure and the physical interpretation of a propagation of perturbations. In linear systems, the information response reduces to the transfer entropy, providing a connection between Fisher and mutual information.

cs.IT

Lagrangian Mechanics of Active Systems

We present a multi-scale modeling and simulation framework for low-Reynolds number hydrodynamics of shape-changing immersed objects, e.g., biological microswimmers and active surfaces. The key idea is to consider principal shape changes as generalized coordinates, and define conjugate generalized hydrodynamic friction forces. Conveniently, the corresponding generalized friction coefficients can be pre-computed and subsequently re-used to solve dynamic equations of motion fast. This framework extends Lagrangian mechanics of dissipative systems to active surfaces and active microswimmers, whose shape dynamics is driven by internal forces. As an application case, we predict in-phase and anti-phase synchronization in pairs of cilia for an experimentally measured cilia beat pattern.

cond-mat.soft

Quantification of Nematic Cell Polarity in Three-dimensional Tissues

How epithelial cells coordinate their polarity to form functional tissues is an open question in cell biology. Here, we characterize a unique type of polarity found in liver tissue, nematic cell polarity, which is different from vectorial cell polarity in simple, sheet-like epithelia. We propose a conceptual and algorithmic framework to characterize complex patterns of polarity proteins on the surface of a cell in terms of a multipole expansion. To rigorously quantify previously observed tissue-level patterns of nematic cell polarity (Morales-Navarette et al., eLife 8:e44860, 2019), we introduce the concept of co-orientational order parameters, which generalize the known biaxial order parameters of the theory of liquid crystals. Applying these concepts to three-dimensional reconstructions of single cells from high-resolution imaging data of mouse liver tissue, we show that the axes of nematic cell polarity of hepatocytes exhibit local coordination and are aligned with the biaxially anisotropic sinusoidal network for blood transport. Our study characterizes liver tissue as a biological example of a biaxial liquid crystal. The general methodology developed here could be applied to other tissues or in-vitro organoids.

q-bio.TO

Chemokinetic scattering, trapping, and avoidance of active Brownian particles

We present a theory of chemokinetic search agents that regulate directional fluctuations according to distance from a target. A dynamic scattering effect reduces the probability to penetrate regions with high fluctuations and thus search success for agents that respond instantaneously to positional cues. In contrast, agents with internal states that initially suppress chemokinesis can exploit scattering to increase their probability to find the target. Using matched asymptotics between the case of diffusive and ballistic search, we obtain analytic results beyond Fox' colored noise approximation.

physics.bio-ph

Bayesian gradient sensing in the presence of rotational diffusion

Biological cells estimate concentration gradients of signaling molecules with a precision that is limited not only by sensing noise, but additionally by the cell's own stochastic motion. We ask for the theoretical limits of gradient estimation in the presence of both motility and sensing noise. We introduce a minimal model of a stationary chemotactic agent in the plane subject to rotational diffusion, which uses Bayesian estimation to optimally infer a gradient direction from noisy concentration measurements. Contrary to the known case of gradient sensing by temporal comparison, we show that for spatial comparison, the ultimate precision of gradient sensing scales not with the rotational diffusion time, but with its square-root. To achieve this precision, an individual agent needs to know its own rotational diffusion coefficient. This agent can accurately estimate the expected variability within an ensemble of agents. If an agent, however, does not account for its own motility noise, Bayesian estimation fails in a characteristic manner.

physics.bio-ph

Renormalization group theory for percolation in time-varying networks

Motivated by multi-hop communication in unreliable wireless networks, we present a percolation theory for time-varying networks. We develop a renormalization group theory for a prototypical network on a regular grid, where individual links switch stochastically between active and inactive states. The question whether a given source node can communicate with a destination node along paths of active links is equivalent to a percolation problem. Our theory maps the temporal existence of multi-hop paths on an effective two-state Markov process. We show analytically how this Markov process converges towards a memory-less Bernoulli process as the hop distance between source and destination node increases. Our work extends classical percolation theory to the dynamic case and elucidates temporal correlations of message losses. Quantification of temporal correlations has implications for the design of wireless communication and control protocols, e.g. in cyber-physical systems such as self-organized swarms of drones or smart traffic networks.

cond-mat.stat-mech

Load response of shape-changing microswimmers scales with their energy efficiency

External forces acting on a microswimmer can feed back on its self-propulsion mechanism. We discuss this load response for a generic microswimmer that swims by cyclic shape changes. We show that the change in cycle frequency is proportional to the Lighthill efficiency of self-propulsion. As a specific example, we consider Najafi's three-sphere swimmer. The force-velocity relation of a microswimmer implies a correction for a formal superposition principle for active and passive motion.

physics.bio-ph

Nonlinear dynamics and fluctuations in biological systems (Habilitation thesis)

The present habilitation thesis in theoretical biological physics addresses two central dynamical processes in cells and organisms: (i) active motility and motility control and (ii) self-organized pattern formation. The unifying theme is the nonlinear dynamics of biological function and its robustness in the presence of strong fluctuations, structural variations, and external perturbations. We theoretically investigate motility control at the cellular scale, using cilia and flagella as ideal model system. Cilia and flagella are highly conserved slender cell appendages that exhibit spontaneous bending waves. This flagellar beat represents a prime example of a chemo-mechanical oscillator, which is driven by the collective dynamics of molecular motors inside the flagellar axoneme. We study the nonlinear dynamics of flagellar swimming, steering, and synchronization, which encompasses shape control of the flagellar beat by chemical signals and mechanical forces. Mechanical forces can synchronize collections of flagella to beat at a common frequency, despite active motor noise that tends to randomize flagellar synchrony. In Chapter 2, we present a new physical mechanism for flagellar synchronization by mechanical self-stabilization that applies to free-swimming flagellated cells. This new mechanism is independent of direct hydrodynamic interactions between flagella. Comparison with experimental data provided by experimental collaboration partners in the laboratory of J. Howard (Yale, New Haven) confirmed our new mechanism in the model organism of the unicellular green alga Chlamydomonas. Further, we characterize the beating flagellum as a noisy oscillator. Using a minimal model of collective motor dynamics, we argue that measured non-equilibrium fluctuations of the flagellar beat result from stochastic motor dynamics at the molecular scale. Noise and mechanical coupling are antagonists ...

q-bio.CB

Optimal decision making for sperm chemotaxis in the presence of noise

For navigation, microscopic agents such as biological cells rely on noisy sensory input. In cells performing chemotaxis, such noise arises from the stochastic binding of signaling molecules at low concentrations. Using chemotaxis of sperm cells as application example, we address the classic problem of chemotaxis towards a single target. We reveal a fundamental relationship between the speed of chemotactic steering and the strength of directional fluctuations that result from the amplification of noise in the chemical input signal. This relation implies a trade-off between slow, but reliable, and fast, but less reliable, steering. By formulating the problem of optimal navigation in the presence of noise as a Markov decision process, we show that dynamic switching between reliable and fast steering substantially increases the probability to find a target, such as the egg. Intriguingly, this decision making would provide no benefit in the absence of noise. Instead, decision making is most beneficial, if chemical signals are above detection threshold, yet signal-to-noise ratios of gradient measurements are low. This situation generically arises at intermediate distances from a target, where signaling molecules emitted by the target are diluted, thus defining a `noise zone' that cells have to cross. Our work addresses the intermediate case between well-studied perfect chemotaxis at high signal-to-noise ratios close to a target, and random search strategies in the absence of navigation cues, e.g. far away from a target. Our specific results provide a rational for the surprising observation of decision making in recent experiments on sea urchin sperm chemotaxis. The general theory demonstrates how decision making enables chemotactic agents to cope with high levels of noise in gradient measurements by dynamically adjusting the persistence length of a biased persistent random walk.

physics.bio-ph

The load-response of the flagellar beat

Cilia and flagella exhibit regular bending waves that perform mechanical work on the surrounding fluid, to propel cellular swimmers and pump fluids inside organisms. Here, we quantify a force-velocity relationship of the beating flagellum, by exposing flagellated \emph{Chlamydomonas} cells to controlled microfluidic flows. A simple theory of flagellar limit-cycle oscillations, calibrated by measurements in the absence of flow, reproduces this relationship quantitatively. We derive a link between the chemo-mechanical efficiency of the flagellar beat and its ability to synchronize to oscillatory flows.

q-bio.CB

Flagellar swimmers oscillate between pusher- and puller-type swimming

Self-propulsion of cellular microswimmers generates flow signatures, commonly classified as pusher- and puller-type, which characterize hydrodynamic interactions with other cells or boundaries. Using experimentally measured beat patterns, we compute that flagellated alga and sperm oscillate between pusher and puller. Beyond a typical distance of 100 um from the swimmer, inertia attenuates oscillatory micro-flows. We show that hydrodynamic interactions between swimmers oscillate in time and are of similar magnitude as stochastic swimming fluctuations.

q-bio.CB