arXiv subjects

Pascal R. Buenzli

Publications and source records attributed to Pascal R. Buenzli.

14 recordsLinked to original sources

arXiv2024

Mechanical cell interactions on curved interfaces

We propose a simple mathematical model to describe the mechanical relaxation of cells within a curved epithelial tissue layer represented by an arbitrary curve in two-dimensional space. This model generalises previous one-dimensional models of flat epithelia to investigate the influence of curvature for mechanical relaxation. We represent the mechanics of a cell body either by straight springs, or by curved springs that follow the curve's shape. To understand the collective dynamics of the cells, we devise an appropriate continuum limit in which the number of cells and the length of the substrate are constant but the number of springs tends to infinity. In this limit, cell density is governed by a diffusion equation in arc length coordinates, where diffusion may be linear or nonlinear depending on the choice of the spring restoring force law. Our results have important implications about modelling cells on curved geometries: (i) curved and straight springs can lead to different dynamics when there is a finite number of springs, but they both converge quadratically to the dynamics governed by the diffusion equation; (ii) in the continuum limit, the curvature of the tissue does not affect the mechanical relaxation of cells within the layer nor their tangential stress; (iii) a cell's normal stress depends on curvature due to surface tension induced by the tangential forces. Normal stress enables cells to sense substrate curvature at length scales much larger than their cell body, and could induce curvature dependences in experiments.

nlin.CG↗

arXiv2024

Random walk models for the propagation of signalling molecules in one-dimensional spatial networks and their continuum limit

The propagation of signalling molecules within cellular networks is affected by network topology, but also by the spatial arrangement of cells in the networks. Understanding the collective reaction--diffusion behaviour in space of signals propagating through cellular networks is an important consideration for example for regenerative signals that convey positional information. In this work, we consider stochastic and deterministic versions of random walk models of signalling molecules propagating and reacting within one-dimensional spatial networks with arbitrary node placement and connectivity. By taking a continuum limit of the random walk models, we derive an inhomogeneous reaction--diffusion--advection equation, where diffusivity and advective velocity depend on local node density and connectivity within the network. Our results show that large spatial variations of molecule concentrations can be induced by heterogeneous node distributions. Furthermore, we find that noise within the stochastic random walk model is directly influenced by node density. We apply our models to consider signal propagation within the osteocyte network of bone, where signals propagating to the bone surface regulate bone formation and resorption processes. We investigate signal-to-noise ratios for different damage detection scenarios and show that the location of perturbations to the network can be detected by signals received at the network boundaries.

cond-mat.dis-nn↗

arXiv2023

Pushing coarse-grained models beyond the continuum limit using equation learning

Mathematical modelling of biological population dynamics often involves proposing high fidelity discrete agent-based models that capture stochasticity and individual-level processes. These models are often considered in conjunction with an approximate coarse-grained differential equation that captures population-level features only. These coarse-grained models are only accurate in certain asymptotic parameter regimes, such as enforcing that the time scale of individual motility far exceeds the time scale of birth/death processes. When these coarse-grained models are accurate, the discrete model still abides by conservation laws at the microscopic level, which implies that there is some macroscopic conservation law that can describe the macroscopic dynamics. In this work, we introduce an equation learning framework to find accurate coarse-grained models when standard continuum limit approaches are inaccurate. We demonstrate our approach using a discrete mechanical model of epithelial tissues, considering a series of four case studies that consider problems with and without free boundaries, and with and without proliferation, illustrating how we can learn macroscopic equations describing mechanical relaxation, cell proliferation, and the equation governing the dynamics of the free boundary of the tissue. While our presentation focuses on this biological application, our approach is more broadly applicable across a range of scenarios where discrete models are approximated by approximate continuum-limit descriptions. All code and data to reproduce this work are available at https://github.com/DanielVandH/StepwiseEQL.jl.

math.DS↗

arXiv2022

Curvature dependences of wave propagation in reaction-diffusion models

Reaction-diffusion waves in multiple spatial dimensions advance at a rate that strongly depends on the curvature of the wave fronts. These waves have important applications in many physical, ecological, and biological systems. In this work, we analyse curvature dependences of travelling fronts in a single reaction-diffusion equation with general reaction term. We derive an exact, non-perturbative curvature dependence of the speed of travelling fronts that arises from transverse diffusion occurring parallel to the wave front. Inward-propagating waves are characterised by three phases: an establishment phase dominated by initial and boundary conditions, a travelling-wave-like phase in which normal velocity matches standard results from singular perturbation theory, and a dip-filling phase where the collision and interaction of fronts create additional curvature dependences to their progression rate. We analyse these behaviours and additional curvature dependences using a combination of asymptotic analyses and numerical simulations.

nlin.PS↗

arXiv2022

Interpreting how nonlinear diffusion affects the fate of bistable populations using a discrete modelling framework

Understanding whether a population will survive and flourish or become extinct is a central question in population biology. One way of exploring this question is to study population dynamics using reaction-diffusion equations, where migration is usually represented as a linear diffusion term, and birth-death is represented with a bistable source term. While linear diffusion is most commonly employed to study migration, there are several limitations of this approach, such as the inability of linear diffusion-based models to predict a well-defined population front. One way to overcome this is to generalise the constant diffusivity, $D$, to a nonlinear diffusivity function $D(C)$, where $C>0$ is the density. While it has been formally established that the choice of $D(C)$ affects long-term survival or extinction of a bistable population, working solely in a classical continuum framework makes it difficult to understand precisely how the choice of $D(C)$ affects survival or extinction. Here, we address this question by working with a simple discrete simulation model that is easy to interpret. The continuum limit of the discrete model is a nonlinear reaction-diffusion equation, where the flux involves a nonlinear diffusion term and the source term is given by the strong Allee effect bistable model. We study population extinction/survival using this very intuitive discrete framework together with numerical solutions of the reaction-diffusion continuum limit equation. This approach provides clear insight into how the choice of $D(C)$ either encourages or suppresses population extinction relative to the classical linear diffusion model.

q-bio.PE↗

arXiv2021

Extinction of bistable populations is affected by the shape of their initial spatial distribution

The question of whether biological populations survive or are eventually driven to extinction has long been examined using mathematical models. In this work we study population survival or extinction using a stochastic, discrete lattice-based random walk model where individuals undergo movement, birth and death events. The discrete model is defined on a two-dimensional hexagonal lattice with periodic boundary conditions. A key feature of the discrete model is that crowding effects are introduced by specifying two different crowding functions that govern how local agent density influences movement events and birth/death events. The continuum limit description of the discrete model is a nonlinear reaction-diffusion equation, and we focus on crowding functions that lead to linear diffusion and a bistable source term that is often associated with the strong Allee effect. Using both the discrete and continuum modelling tools we explore the complicated relationship between the long-term survival or extinction of the population and the initial spatial arrangement of the population. In particular, we study different spatial arrangements of initial distributions: (i) a well-mixed initial distribution where the initial density is independent of position in the domain; (ii) a vertical strip initial distribution where the initial density is independent of vertical position in the domain; and, (iii) several forms of two-dimensional initial distributions where the initial population is distributed in regions with different shapes. Our results indicate that the shape of the initial spatial distribution of the population affects extinction of bistable populations. All software required to solve the discrete and continuum models used in this work are available on GitHub.

q-bio.PE↗

arXiv2017

Late stages of mineralisation and their signature on the bone mineral density distribution

Purpose: Experimental measurements of bone mineral density distributions (BMDDs) enable a determination of secondary mineralisation kinetics in bone, but the maximum degree of mineralisation and how this maximum is approached remain uncertain. We thus test computationally different hypotheses on late stages of bone mineralisation by simulating BMDDs in low turnover conditions. Materials and Methods: An established computational model of the BMDD that accounts for mineralisation and remodelling processes was extended to limit mineralisation to various maximum calcium capacities of bone. Simulated BMDDs obtained by reducing turnover rate from the reference trabecular BMDD under different assumptions on late stage mineralisation kinetics were compared with experimental BMDDs of low-turnover bone. Results: Simulations show that an abrupt stopping of mineralisation near a maximum calcium capacity induces a pile-up of minerals in the BMDD statistics that is not observed experimentally. With a smooth decrease of mineralisation rate, imposing low maximum calcium capacities helps to match peak location and width of simulated low turnover BMDDs with peak location and width of experimental BMDDs, but results in a distinctive asymmetric peak shape. No tuning of turnover rate and maximum calcium capacity was able to explain the differences found in experimental BMDDs between trabecular bone (high turnover) and femoral cortical bone (low turnover). Conclusions: Secondary mineralisation in human bone does not stop abruptly, but continues slowly up to a calcium content greater than 30 wt% Ca. The similar mineral heterogeneity seen in trabecular and femoral cortical bones at different peak locations was unexplained by turnover differences tested.

q-bio.CB↗

arXiv2016

Governing equations of tissue modelling and remodelling: A unified generalised description of surface and bulk balance

Several biological tissues undergo changes in their geometry and in their bulk material properties by modelling and remodelling processes. Modelling synthesises tissue in some regions and removes tissue in others. Remodelling overwrites old tissue material properties with newly formed, immature tissue properties. As a result, tissues are made up of different "patches", i.e., adjacent tissue regions of different ages and different material properties, within evolving boundaries. In this paper, generalised equations governing the spatio-temporal evolution of such tissues are developed within the continuum model. These equations take into account nonconservative, discontinuous surface mass balance due to creation and destruction of material at moving interfaces, and bulk balance due to tissue maturation. These equations make it possible to model patchy tissue states and their evolution without explicitly maintaining a record of when/where resorption and formation processes occurred. The time evolution of spatially averaged tissue properties is derived systematically by integration. These spatially-averaged equations cannot be written in closed form as they retain traces that tissue destruction is localised at tissue boundaries. The formalism developed in this paper is applied to bone tissues, which exhibit strong material heterogeneities due to their slow mineralisation and remodelling processes. Evolution equations are proposed in particular for osteocyte density and bone mineral density. Effective average equations for bone mineral density (BMD) and tissue mineral density (TMD) are derived using a mean-field approximation. The error made by this approximation when remodelling patchy tissue is investigated. The specific time signatures of BMD or TMD during remodelling events may provide a way to detect these events occurring at lower, unseen spatial resolutions from microCT scans.

q-bio.TO↗

arXiv2013

Bone refilling in cortical bone multicellular units: Insights into tetracycline double labelling from a computational model

Bone remodelling is carried out by `bone multicellular units' (BMUs) in which active osteoclasts and active osteoblasts are spatially and temporally coupled. The refilling of new bone by osteoblasts towards the back of the BMU occurs at a rate that depends both on the number of osteoblasts and on their secretory activity. In cortical bone, a linear phenomenological relationship between matrix apposition rate (MAR) and BMU cavity radius is found experimentally. How this relationship emerges from the combination of complex, nonlinear regulations of osteoblast number and secretory activity is unknown. Here, we extend our previous mathematical model of cell development within a single BMU to investigate how osteoblast number and osteoblast secretory activity vary along the BMU's closing cone. MARs predicted by the model are compared with data from tetracycline double labelling experiments. We find that the linear phenomenological relationship observed in these experiments between MAR and BMU cavity radius holds for most of the refilling phase simulated by our model, but not near the start and end of refilling. This suggests that at a particular bone site undergoing remodelling, bone formation starts and ends rapidly. Our model also suggests that part of the observed cross-sectional variability in tetracycline data may be due to different bone sites being refilled by BMUs at different stages of their lifetime. The different stages of a BMU's lifetime depend on whether the cell populations within the BMU are still developing or have reached a quasi-steady state while travelling through bone. We find that due to their longer lifespan, active osteoblasts reach a quasi-steady distribution more slowly than active osteoclasts. We suggest that this fact may locally enlarge the Haversian canal diameter (due to a local lack of osteoblasts compared to osteoclasts) near the BMU's point of origin.

q-bio.TO↗

arXiv2012

Endocortical bone loss in osteoporosis: The role of bone surface availability

Age-related bone loss and postmenopausal osteoporosis are disorders of bone remodelling, in which less bone is reformed than resorbed. Yet, this dysregulation of bone remodelling does not occur equally in all bone regions. Loss of bone is more pronounced near and at the endocortex, leading to cortical wall thinning and medullary cavity expansion, a process sometimes referred to as "trabecularisation" or "cancellisation". Cortical wall thinning is of primary concern in osteoporosis due to the strong deterioration of bone mechanical properties that it is associated with. In this paper, we examine the possibility that the non-uniformity of microscopic bone surface availability could explain the non-uniformity of bone loss in osteoporosis. We use a computational model of bone remodelling in which microscopic bone surface availability influences bone turnover rate and simulate the evolution of the bone volume fraction profile across the midshaft of a long bone. We find that bone loss is accelerated near the endocortical wall where the specific surface is highest. Over time, this leads to a substantial reduction of cortical wall thickness from the endosteum. The associated expansion of the medullary cavity can be made to match experimentally observed cross-sectional data from the Melbourne Femur Collection. Finally, we calculate the redistribution of the mechanical stresses in this evolving bone structure and show that mechanical load becomes critically transferred to the periosteal cortical bone.

q-bio.TO↗

arXiv2012

Modelling the anabolic response of bone using a cell population model

To maintain bone mass during bone remodelling, coupling is required between bone resorption and bone formation. This coordination is achieved by a network of autocrine and paracrine signalling molecules between cells of the osteoclast lineage and cells of the osteoblastic lineage. Mathematical modelling of signalling between cells of both lineages can assist in the interpretation of experimental data, clarify signalling interactions and help develop a deeper understanding of complex bone diseases. In this paper, we further develop a mathematical model of bone cell interactions by Pivonka et al. (2008) to include the proliferation of precursor osteoblasts into the model. This inclusion is important to be able to account for Wnt signalling, believed to play an important role in anabolic responses of bone. We show that an increased rate of differentiation to precursor cells or an increased rate of proliferation of precursor osteoblasts themselves both result in increased bone mass. However, modelling these different processes separately enables the new model to represent recent experimental discoveries such as the role of Wnt signalling in bone biology and the recruitment of osteoblast progenitor cells by transforming growth factor β. Finally, we illustrate the power of the new model's capabilities by applying the model to prostate cancer metastasis to bone. In the bone microenvironment, prostate cancer cells are believed to release some of the same signalling molecules used to coordinate bone remodelling (i.e. Wnt and PTHrP), enabling the cancer cells to disrupt normal signalling and coordination between bone cells. This disruption can lead to either bone gain or bone loss. We demonstrate that the new computational model developed here is capable of capturing some key observations made on the evolution of the bone mass due to metastasis of prostate cancer to the bone microenvironment

q-bio.TO↗

arXiv2012

The influence of bone surface availability in bone remodelling - A mathematical model including coupled geometrical and biomechanical regulations of bone cells

Bone is a biomaterial undergoing continuous renewal. The renewal process is known as bone remodelling and is operated by bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Both biochemical and biomechanical regulatory mechanisms have been identified in the interaction between osteoclasts and osteoblasts. Here we focus on an additional and poorly understood potential regulatory mechanism of bone cells, that involves the morphology of the microstructure of bone. Bone cells can only remove and replace bone at a bone surface. However, the microscopic availability of bone surface depends in turn on the ever-changing bone microstructure. The importance of this geometrical dependence is unknown and difficult to quantify experimentally. Therefore, we develop a sophisticated mathematical model of bone cell interactions that takes into account biochemical, biomechanical and geometrical regulations. We then investigate numerically the influence of bone surface availability in bone remodelling within a representative bone tissue sample. The interdependence between the bone cells' activity, which modifies the bone microstructure, and changes in the microscopic bone surface availability, which in turn influences bone cell development and activity, is implemented using a remarkable experimental relationship between bone specific surface and bone porosity. Our model suggests that geometrical regulation of the activation of new remodelling events could have a significant effect on bone porosity and bone stiffness. On the other hand, geometrical regulation of late stages of osteoblast and osteoclast differentiation seems less significant. We conclude that the development of osteoporosis is probably accelerated by this geometrical regulation in cortical bone, but probably slowed down in trabecular bone.

q-bio.TO↗

arXiv2007

Thermal quantum electrodynamics of nonrelativistic charged fluids

The theory relevant to the study of matter in equilibrium with the radiation field is thermal quantum electrodynamics (TQED). We present a formulation of the theory, suitable for non relativistic fluids, based on a joint functional integral representation of matter and field variables. In this formalism cluster expansion techniques of classical statistical mechanics become operative. They provide an alternative to the usual Feynman diagrammatics in many-body problems which is not perturbative with respect to the coupling constant. As an application we show that the effective Coulomb interaction between quantum charges is partially screened by thermalized photons at large distances. More precisely one observes an exact cancellation of the dipolar electric part of the interaction, so that the asymptotic particle density correlation is now determined by relativistic effects. It has still the $r^{-6}$ decay typical for quantum charges, but with an amplitude strongly reduced by a relativistic factor.

quant-ph↗

arXiv2006

Equilibrium correlations in charged fluids coupled to the radiation field

We provide an exact microscopic statistical treatment of particle and field correlations in a system of quantum charges in equilibrium with a classical radiation field. Using the Feynman-Kac-Ito representation of the Gibbs weight, the system of particles is mapped onto a collection of random charged wires. The field degrees of freedom can be integrated out, providing an effective pairwise magnetic potential. We then calculate the contribution of the transverse field coupling to the large-distance particle correlations. The asymptotics of the field correlations in the plasma are also exactly determined.

cond-mat.stat-mech↗