Biology subjects

Muenker, T. M.

Publications and source records attributed to Muenker, T. M..

5 recordsLinked to original sources

bioRxiv2025

Direct mechanical communication of cellular to nuclear shape in oocytes

The mechanical properties of the cytoplasm and nucleoplasm are crucial for the correct and robust functioning of a cell and play a key role in understanding how mechanical signals are transferred to the nucleus. Here, we demonstrate remarkable shape mimicry between the cellular and nuclear shape of oocytes, following the externally applied deformation without direct contact between the cell cortex and the nucleus. This effect arises from a surprisingly soft and fluid-like nucleoplasm that is barely resisting any external strain, while the viscoelastic cytoplasm drives shape transmission. Comparative studies in jellyfish, starfish, and mouse oocytes reveal that lower cytoplasmic elasticity in jellyfish leads to reduced nuclear shape mimicry, highlighting the role of cytoplasmic mechanics in nuclear deformation. Significance StatementMechanosensing of the nucleus is, in addition to chemical signalling, an important factor in gene expression. Although nuclei are often thought to be rigid inclusions in the cytoplasm of a cell, we show that in oocytes nuclei are much more deformable. Using a combination of intranuclear, intracellular and extracellular measurements, we attribute our findings to a fine balance between the soft nucleoplasm surrounded by an elastic shell and the viscoelastic properties of the cytoplasm.

biophysics↗

bioRxiv2023

Intracellular mechanical fingerprint reveals cell type specific mechanical tuning

Living cells are complex entities that perform various tasks with astonishing robustness. While the direct dependence of biological processes on controlled protein expression is well established, we have only begun to understand how intracellular mechanical characteristics guide and support biological function. This is in stark contrast to the expected functional role that intracellular mechanical properties should have for many core cellular functions such as organization, homeostasis, and transport. From a mechanical point of view, cells are complex viscoelastic materials that are continuously driven out of thermodynamic equilibrium, which makes both a physical measurement and mathematical modeling of their properties difficult. Here, we define a "mechanical fingerprint" that can not only characterize the intracellular mechanical state, but also carve out the mechanical differences between cell types with the potential to relate these to proper cell function. By analyzing the frequency-dependent viscoelastic properties and intracellular activity of cells using microrheology, we distilled the complex active mechanical state into just 6 parameters that comprise the mechanical fingerprint. The systematic investigation of the fingerprint illustrates a parameter tuning that could be related to functional cellular requirements. However, the full potential of the mechanical fingerprint is given by a statistical analysis of its parameters across all investigated cell types, which suggests that cells can modify mechanical parameters in a correlated way to position their intracellular mechanical properties within a well-defined phase-space that is spanned between activity, mechanical resistance, and fluidity. This paves the way for a systematic study of the interdependence of biological function and intracellular active mechanics.

biophysics↗

bioRxiv2022

Dystrophin is a mechanical tension modulator

Duchenne muscular dystrophy (DMD) represents the most common inherited muscular disease, where progressing muscle weakness leads to loss of ambulation and premature death. DMD is caused by mutations in the dystrophin gene, and is known to reduce the contractile capacity of muscle tissue both in vivo, and in reconstituted systems in vitro. However, these observations are based on mechanical studies that focused on stimulated contractions of skeletal muscle tissue. Seemingly paradoxical, upon evaluating bioengineered skeletal muscles produced from DMD patient derived myoblasts we observe an increase in myosin motor mediated homeostatic tissue tension that strongly correlates with decreased stimulated tissue strength, suggesting the involvement of dystrophin in regulating the baseline homeostatic tension level of tissue. This was confirmed by three independent pairs of isogenic cell lines, one of each lacking dystrophin compared to the isogenic dystrophin-expressing control. From this we speculate that the protective function of dystrophin also supports cellular fitness via active participation in the mechanosensation to achieve and sustain an ideal level of tissue tension. Hence, this study reveals fundamental novel insights into skeletal muscle biomechanics and into a new key mechanical aspect of DMD pathogenesis, provided by increased homeostatic tissue tension.

biophysics↗

bioRxiv2022

Onsager regression characterizes living systems in passive measurements

Understanding life is arguably among the most complex scientific problems faced in modern research. From a physics perspective, living systems are complex dynamic entities that operate far from thermodynamic equilibrium.1-3 This active, non-equilibrium behaviour, with its constant hunger for energy, allows life to overcome the ever dispersing forces of entropy, and drives cellular organisation.4, 5 Unfortunately, most analysis methods provided by the toolbox of statistical mechanics cannot be used in such non-equilibrium situations, forcing researchers to use sophisticated and often invasive approaches to study the mechanistic processes inside living organisms. Here we introduce a new observable coined the mean back relaxation. Based on three-point probabilities, and exploiting Onsagers regression hypothesis, it extracts additional information from passively observed trajectories compared to classical observables such as the mean squared displacement. We mathematically prove that the mean back relaxation is able to detect broken detailed balance in systems confined in stationary or actively diffusing potentials. We show in experiment and theory that it gives access to the non-equilibrium generating energy and the viscoelastic material properties of a well controlled artificial system, and we experimentally demonstrate that it does so even for a variety of living systems, revealing an astonishing relation between the mean back relaxation and the active mechanical energy. Based on these findings, we conclude that it acts as a new marker of non-equilibrium dynamics. Combining, in a next step, passive fluctuations with the extracted active energy allows to overcome a fundamental barrier in the study of living systems; it gives access to the viscoelastic material properties from passive measurements.

biophysics↗

bioRxiv2020

Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis

The mechanical properties and tension of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue development a key requirement to advance our understanding of muscle function and development. Recently developed elastic in vitro culture chambers allow for raising 3D muscle tissue under controlled conditions and measurements of tissue force generation. However, these chambers are inherently incompatible with high resolution microscopy limiting their usability to global force measurements, and preventing the exploitation of modern fluorescence based investigation methods for live and dynamic measurements. Here we present a new chamber design pairing global force measurements, quantified from post deflection, with local tension measurements obtained from elastic hydrogel beads embedded in the muscle tissue. High resolution 3D video microscopy of engineered muscle development, enabled by the new chamber, shows an early mechanical tissue homeostasis that remains stable in spite of continued myotube maturation.Competing Interest StatementTB and AH have filed a patent for the presented chamber system.View Full Text

biophysics↗