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Timo Betz

Publications and source records attributed to Timo Betz.

13 recordsLinked to original sources

A Physics-Flavored Transformer Network for Parametrizing Contraction Dynamics of Engineered Skeletal Muscle Tissues

Engineered Skeletal Muscle Tissues (ESMs) have become a key structure for biomedical disease modeling and pharmacological screening, yet their functional characterization often relies on simplistic metrics like peak force, discarding critical kinetic information. This is partially due to the high level of mathematical complexity which mechanistic models introduce to capture these dynamics. Hence, exactly the complexity prevents scalable application and widespread adaptation in the field. Here we present a Physics-Flavored Neural Network (PFNN) that automates the kinetic phenotyping of ESMs. Our architecture integrates a stretched-exponential physical model into a CNN-Transformer, enabling the extraction of physically meaningful parameters directly from force-time profiles. To address the scarcity of labeled biological data, we employ a hybrid training paradigm: the model develops a "physical intuition" on synthetic data before undergoing unsupervised self-alignment on unlabeled real-world measurements. Our results demonstrate that this physics-flavored approach achieves high-fidelity parameterization across diverse contractile phenotypes and cell lines, including Duchenne Muscular Dystrophy models. Our scalable, self-improving pipeline bridges the gap between idealized biophysics and noisy \emph{in vitro} data, providing a robust tool for high-throughput biophysical research.

cs.LG

Self-propelled particles driven by light

Recent advances in the field of active soft matter promise a lot. Both, experimental advances and theoretical understanding point towards new material classes in reach, for example self-healing materials that might switch their properties from elastic to solid easily or switch their macroscopic shapes. All these materials require an active force to propel parts of themselves on the micrometer scale. While chemical fuels are often used to generate these active forces, applying energy in a simple and continuous way remains unsolved. Here we explore using light as such an energy source. Overall, generating active driven, self-propelled particles is hence not only of great interest but also a general challenge. Moreover, controlling such particles even within living tissue would open new worlds, for example to enable specific drug delivery or the design of micro-robots. One recently proposed method to establish light driven self propelled particles is to create specific shaped and transparent objects, that move when illuminated with homogeneous light. In these particles, the refraction of the light leads to a momentum transfer, which then drives the active movement. Here, we show both in simulation and experiments that the production of such particles is possible and demonstrate the feasibility of this propulsion effect, while investigating different shapes. Our experiments show that breaking the shape-symmetry of the particles creates a refraction-based propulsion under homogeneous illumination. Subsequent simulations reveal that total reflection leads to the largest momentum transfer among all different geometries considered. Overall, our study introduces the proof-of-principle for refraction-propelled particles, which has the potential to benefit many fields of study including cellular behaviour, collective dynamics and the understanding of disease mechanisms.

physics.bio-ph

Time reversal breaking of colloidal particles in cells

We investigate signatures of broken time reversal symmetry in stochastic trajectory data, employing the previously introduced three point correlation called mean back relaxation. We specifically investigate data from a simple driven model, as well as from colloidal particles within living or passivated biological cells. Both in the model as well as in cell data, MBR detects broken time reversal symmetry, and furthermore, allows to determine relevant time and length scales of activity. For the cells, we show, by applying various drugs, that it is predominantly the presence of microtubules which is needed for a time reversal symmetry breaking. We employ a bound for entropy production, finding that it is in striking relation to previously determined active energies that quantify violation of the fluctuation dissipation theorem.

cond-mat.soft

Evaluating non-equilibrium trajectories via mean back relaxation: Dependence on length and time scales

The mean back relaxation (MBR) relates the value of a stochastic process at three different time points. It has been shown to detect broken detailed balance under certain conditions. For experiments of probe particles in living and passivated cells, MBR was found to be related to the so called effective energy, which quantifies the violation of the fluctuation dissipation theorem. In this manuscript, we discuss the dependence on the length and time parameters that enter MBR, both for cells as well as for a model system, finding qualitative agreement between the two. For the cell data, we extend the phenomenological relation between MBR and effective energy to a larger range of time parameters compared to previous work, allowing to test it in systems with limited resolution. We analyze the variance of back relaxation (VBR) in dependence of the mentioned parameters, relevant for the statistical error in MBR evaluation. For Gaussian systems, the variance is found analytically in terms of the mean squared displacement, and we determine its absolute minimum as a function of the length and time parameters. Comparing VBR from cell data to a Gaussian prediction demonstrates a non-Gaussian process.

cond-mat.stat-mech

Active Intracellular Mechanics: A Key to Cellular Function and Organization

While mechanobiology has demonstrated that precise control over mechanical properties at the whole-cell level is crucial for many biological functions, comparatively little attention has been paid to the intracellular mechanical properties. Experimental tools have only recently become available to adequately measure the viscoelasticity and activity of the cytosol, revealing, revealing that the active, non-equilibrium nature of the intracellular environment must be carefully considered. To explore the interplay between active forces and viscoelastic properties, it is helpful to consider our current understanding of intracellular active mechanics. In this review, we aim not only to provide an intuitive and quantitative introduction to the relevant physical concepts, but also to offer an overview of the proteins that establish intracellular active mechanics, highlighting their spatial and temporal variation with a particular focus on the role of activity. Although we are only beginning to uncover the importance of intracellular active mechanics for cellular mechanisms, it is increasingly clear that these properties must be precisely regulated to ensure proper cellular function.

q-bio.SC

Traction force microscopy for linear and nonlinear elastic materials as a parameter identification inverse problem

Traction force microscopy is a method widely used in biophysics and cell biology to determine forces that biological cells apply to their environment. In the experiment, the cells adhere to a soft elastic substrate, which is then deformed in response to cellular traction forces. The inverse problem consists in computing the traction stress applied by the cell from microscopy measurements of the substrate deformations. In this work, we consider a linear model, in which 3D forces are applied at a 2D interface, called 2.5D traction force microscopy, and a nonlinear pure 2D model, from which we directly obtain a linear pure 2D model. All models lead to a linear resp. nonlinear parameter identification problem for a boundary value problem of elasticity. We analyze the respective forward operators and conclude with some numerical experiments for simulated and experimental data.

math.NA

AdoptODE: Fusion of data and expert knowledge for modeling dynamical systems

Building a representative model of a complex system remains a highly challenging problem. While by now there is basic understanding of most physical domains, model design is often hindered by lack of detail, for example concerning model dimensions or its relevant constraints. Here we present a novel model-building approach -- adoptODE -- augmenting basic system descriptions, based on expert knowledge in the form of ordinary differential equations, with continuous adjoint sensitivity analysis related to artificial neural network principles, based on observable data. With this we have created a general tool, that can be applied to any physical system described by ordinary differential equations. AdoptODE allows validating or extending the initial description, for example with different variables and constraints. This way one arrives at a better-optimised, representative low-dimensional model, which can fit existing data and predict novel experimental outcomes. We validate our method on five, quite different problem domains. (1) Kolmogorov model: Lotka Volterra model where we show the application of adoptODE to continuous-time Markov processes and the performance of adoptODE when working with noisy data. (2) Particle model: Interactive N-body, is a demonstration of the scalability of adoptODE and that even interactive system with a high number of elements can be reconstructed with high precision. (3) Excitable media (heart dynamics) by the Bueno\-Orovio\-Cherry\-Fenton model: AdoptODE can reconstruct the parameters of a high-dimensional model and fields for diffusion driven system for chaotic behaviour. (4) Fluid dynamics: Rayleigh-B\'enard Convection where a complete unknown field, the temperature, can be extracted from only velocity data. (5) New experimental data of Zebrafish embryogenesis: This is a case where we extend existing models with new variables.

physics.data-an

Entropy bound for time reversal markers

We derive a bound for entropy production in terms of the mean of normalizable path-antisymmetric observables. The optimal observable for this bound is shown to be the signum of entropy production, which is often easier determined or estimated than entropy production itself. It can be preserved under coarse graining by use of a simple path grouping algorithm. We demonstrate this relation and its properties using a driven network on a ring, for which the bound saturates for short times for any driving strength. This work can open a way to systematic coarse graining of entropy production.

cond-mat.stat-mech

Roadmap for Optical Tweezers

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nanoparticle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration.

physics.optics

Fluctuations of a membrane nanotube covered with an actin sleeve

Many biological functions rely on the reshaping of cell membranes, in particular into nanotubes, which are covered in vivo by dynamic actin networks. Nanotubes are subject to thermal fluctuations, but the effect of these on cell functions is unknown. Here, we form nanotubes from liposomes using an optically trapped bead adhering to the liposome membrane. From the power spectral density of this bead, we study the nanotube fluctuations in the range of membrane tensions measured in vivo. We show that an actin sleeve covering the nanotube damps its high frequency fluctuations because of the network viscoelasticity. Our work paves the way for further studies on the effect of nanotube fluctuations in cellular functions.

physics.bio-ph

Fluctuations in active membranes

Active contributions to fluctuations are a direct consequence of metabolic energy consumption in living cells. Such metabolic processes continuously create active forces, which deform the membrane to control motility, proliferation as well as homeostasis. Membrane fluctuations contain therefore valuable information on the nature of active forces, but classical analysis of membrane fluctuations has been primarily centered on purely thermal driving. This chapter provides an overview of relevant experimental and theoretical approaches to measure, analyze and model active membrane fluctuations. In the focus of the discussion remains the intrinsic problem that the sole fluctuation analysis may not be sufficient to separate active from thermal contributions, since the presence of activity may modify membrane mechanical properties themselves. By combining independent measurements of spontaneous fluctuations and mechanical response, it is possible to directly quantify time and energy-scales of the active contributions, allowing for a refinement of current theoretical descriptions of active membranes.

physics.bio-ph

Nonequilibrium dissipation in living oocytes

Living organisms are inherently out-of-equilibrium systems. We employ new developments in stochastic energetics and rely on a minimal microscopic model to predict the amount of mechanical energy dissipated by such dynamics. Our model includes complex rheological effects and nonequilibrium stochastic forces. By performing active microrheology and tracking micron-sized vesicles in the cytoplasm of living oocytes, we provide unprecedented measurements of the spectrum of dissipated energy. We show that our model is fully consistent with the experimental data, and we use it to offer predictions for the injection and dissipation energy scales involved in active fluctuations.

q-bio.SC

Active mechanics reveal molecular-scale force kinetics in living oocytes

Active diffusion of intracellular components is emerging as an important process in cell biology. This process is mediated by complex assemblies of molecular motors and cytoskeletal filaments that drive force generation in the cytoplasm and facilitate enhanced motion. The kinetics of molecular motors have been precisely characterized in-vitro by single molecule approaches, however, their in-vivo behavior remains elusive. Here, we study the active diffusion of vesicles in mouse oocytes, where this process plays a key role in nuclear positioning during development, and combine an experimental and theoretical framework to extract molecular-scale force kinetics (force, power-stroke, and velocity) of the in-vivo active process. Assuming a single dominant process, we find that the nonequilibrium activity induces rapid kicks of duration $\tau \sim$ 300 $\mu$s resulting in an average force of $F \sim$ 0.4 pN on vesicles in in-vivo oocytes, remarkably similar to the kinetics of in-vitro myosin-V. Our results reveal that measuring in-vivo active fluctuations allows extraction of the molecular-scale activity in agreement with single-molecule studies and demonstrates a mesoscopic framework to access force kinetics.

physics.bio-ph