Biology subjects

Oelz, D. B.

Publications and source records attributed to Oelz, D. B..

8 recordsLinked to original sources

bioRxiv2025

Non-uniform filament turnover and mechanically-driven contractility and bundle formation in disordered actomyosin networks

Bundles of actin filaments with similar positions and orientations commonly occur in cytoskeletal networks. We use mathematical modelling and simulation to investigate how filament turnover and mechanics influence contractility and bundle formation in disordered actomyosin networks. Using a two-dimensional agent-based model for an actomyosin network, we investigate four simplified models for filament turnover: uniform, biased, branching, and treadmilling. With no turnover, over time contractility decreases and bundle formation increases, and networks eventually form stationary patterns that cannot contract. Introducing turnover allows contractility to persist longer compared to the no-turnover scenario. Uniform turnover, where new filaments have random positions and orientations, disrupts bundle formation and enables persistent contractility. In biased turnover, branching, and treadmilling, the positions and orientations of new filaments depend on the existing network. These non-uniform turnover models increase bundle formation compared to uniform turnover, while still allowing long-term contractility. Branching at 70{degrees} disrupts bundle formation to enable prolonged contractility, whereas filament treadmilling disrupts the trade-off between bundle formation and contractility. Biased turnover places new filaments near existing ones, which promotes bundle formation but is less effective at maintaining contractility. We also varied mechanical factors in our simulations, especially filament bending flexibility and protein friction, which enhance bundle formation and contractility, respectively. Our results suggest that variations in turnover and mechanics might allow cells to tune contractility and bundle formation in disordered actomyosin networks.

biophysics↗

bioRxiv2024

Mechanochemical Patterning Localizes the Organizer of a Luminal Epithelium

The spontaneous emergence of tissue patterns is often attributed to biochemical reaction-diffusion systems. In Hydra tissue regeneration, the formation of a Wnt signaling center serves as a well-known example of such a process. However, despite extensive research, a strictly biochemical mechanism for self-organization in Hydra remains elusive. In this study, we investigated mechanical stimuli and identified a positive feedback loop between Wnt signaling and tissue stretching. We developed a mathematical model of mechanochemical pattern formation in a closed elastic shell, representing regenerating Hydra epithelial spheroids. Our model explains how mechanical forces drive axis formation and predicts the organizers location under various perturbations, providing a more comprehensive understanding of the spatial dynamics involved. Validation by partially confining regenerating tissues showed that the organizer indeed forms in regions with the greatest stretching potential. This work highlights a novel mechanochemical mechanism for luminal epithelium patterning, suggesting that mechanical forces, in addition to biochemical signals, play a crucial role in tissue regeneration and axis specification. Our findings offer broader implications for the role of mechanical forces in tissue organization in various biological systems, opening new avenues for investigating mechanochemical feedback in development and regeneration.

developmental biology↗

bioRxiv2024

Stretch-induced recruitment of myosin into transversal actin rings stabilizes axonal large cargo transport

We study the axonal transport of large cargo vesicles and its feedback with contractile transversal actomyosin rings in axons through modelling and simulation. To this end, we simulate a mathematical model that integrates forces generated by the molecular motors and forces exerted by transversal actin rings. Our results predict that cargo vesicles exhibit bidirectional movement along with pauses in agreement with observations. It has been observed that during predominantly retrograde axonal cargo transport, blebbistatin treatment prolongs the periods spent by the cargo in anterograde transport. Our simulations show that this can be explained by mechanotransductive stretch-induced recruitment of myosin motors into transversal actin rings. These findings offer valuable insights into the complex dynamics of axonal cargo transport and propose potential avenues for further experimental research.

biophysics↗

bioRxiv2023

A mathematical model for axonal transport of large cargo vesicles

In this study, we consider axonal transport of large cargo vesicles characterised by transient expansion of the axon shaft. Our goal is to formulate a mathematical model which captures the dynamic mechanical interaction of such cargo vesicles with the membrane associated periodic cytoskeletal structure (MPS). It consists of regularly spaced actin rings that are transversal to the longitudinal direction of the axon and involved in the radial contraction of the axon. A system of force balance equations is formulated by which we describe the transversal rings as visco-elastic Kelvin-Voigt elements. In a homogenisation limit, we reformulate the model as a free boundary problem for the interaction of the submembranous MPS with the large vesicle. We derive a non-linear force-velocity relation as a quasi-steady state solution. Computationally we analyse the vesicle size dependence of the transport speed and use an asymptotic approximation to formulate it as a power law that can be tested experimentally.

biophysics↗

bioRxiv2022

A Microtubule Mechanostat Enables Cells to Navigate Confined Environments

Cells migrating through complex 3D environments experience considerable physical challenges including tensile stress and compression. To move, cells need to resist these forces whilst also squeezing the large nucleus through confined spaces. This requires highly coordinated cortical contractility. Microtubules can both resist compressive forces and sequester key actomyosin regulators to ensure appropriate activation of contractile forces. Yet, how these two roles are integrated to achieve nuclear transmigration in 3D is largely unknown. Here, we demonstrate that compression triggers reinforcement of a dedicated microtubule structure at the rear of the nucleus by the mechanoresponsive recruitment of CLASPs (cytoplasmic linker-associated proteins) which dynamically strengthens and repairs the lattice. These reinforced microtubules form the mechanostat: an adaptive feedback mechanism that allows the cell to both withstand compressive force and spatiotemporally organise contractility signalling pathways. The microtubule mechanostat facilitates nuclear positioning and coordinates force production to enable the cell to pass through constrictions. Disruption of the mechanostat imbalances cortical contractility, stalling migration and ultimately resulting in catastrophic cell rupture. Our findings reveal a new role for microtubules as cellular sensors which detect and respond to compressive forces, enabling movement and ensuring survival in mechanically demanding environments. One Sentence SummaryMechanically tuned microtubules form a mechanostat to coordinate contractility and nuclear positioning in confined migration.

cell biology↗

bioRxiv2021

F-actin bending facilitates net actomyosin contraction by inhibiting expansion with plus-end-located myosin motors

Contraction of actomyosin networks underpins important cellular processes including motility and division. The mechanical origin of actomyosin contraction is not fully-understood. We investigate whether contraction arises on the scale of individual filaments, without needing to invoke network-scale interactions. We derive discrete force-balance and continuum partial differential equations for two symmetric, semi-flexible actin filaments with an attached myosin motor. Assuming the system exists within a homogeneous background material, our method enables computation of the stress tensor, providing a measure of contractility. After deriving the model, we use a combination of asymptotic analysis and numerical solutions to show how F-actin bending facilitates contraction on the scale of two filaments. Rigid filaments exhibit polarity-reversal symmetry as the motor travels from the minus to plus-ends, such that contractile and expansive components cancel. Filament bending induces a geometric asymmetry that brings the filaments closer to parallel as a myosin motor approaches their plus-ends, decreasing the effective spring force opposing motor motion. The reduced spring force enables the motor to move faster close to filament plus-ends, which reduces expansive stress and gives rise to net contraction. Bending-induced geometric asymmetry provides both new understanding of actomyosin contraction mechanics, and a hypothesis that can be tested in experiments.

biophysics↗

bioRxiv2021

Spatial redistribution of neurosecretory vesicles upon stimulation accelerates their directed transport to the plasma membrane

Through the integration of results from an imaging analysis of intracellular trafficking of labelled neurosecretory vesicles in chromaffin cells, we develop a Markov state model to describe their transport and binding kinetics. Our simulation results indicate that a spatial redistribution of neurosecretory vesicles occurs upon secretagogue stimulation leading vesicles to the plasma membrane where they undergo fusion thereby releasing adrenaline and noradrenaline. Furthermore, we find that this redistribution alone can explain the observed up-regulation of vesicle transport upon stimulation and its directional bias towards the plasma membrane. Parameter fitting indicates that in the deeper compartment within the cell, vesicle transport is asymmetric and characterised by a bias towards the plasma membrane. We also find that crowding of neurosecretory vesicles undergoing directed transport explains the observed accelerated recruitment of freely diffusing vesicles into directed transport upon stimulation.

cell biology↗

bioRxiv2021

Protein Friction and Filament Bending Facilitate Contraction of Disordered Actomyosin Networks

We use mathematical modelling and computation to investigate how protein friction facilitates contraction of disordered actomyosin networks. We simulate two-dimensional networks using an agent-based model, consisting of a system of force-balance equations for myosin motor proteins and semi-flexible actin filaments. A major advantage of our approach is that it enables direct calculation of the network stress tensor, which provides a quantitative measure of contractility. Exploiting this, we use repeated simulations of disordered networks to confirm that both protein friction and actin filament bending are required for contraction. We then use simulations of elementary two-filament assemblies to show that filament bending flexibility can generate contraction on the microscopic scale. Finally, we show that actin filament turnover is necessary to sustain contraction and prevent pattern formation. Simulations with and without turnover also exhibit contractile pulses. However, these pulses are aperiodic, suggesting that periodic pulsation can only be achieved by additional regulatory mechanisms.

biophysics↗