Réunion d'hiver SMC 2024

Vancouver/Richmond, 29 novembre - 2 decembre 2024

       

From single to collective cell migration: A geometric multi-physics bulk-surface PDE approach
Org: Anotida Madzvamuse (University of British Columbia) et Stephanie Portet (University of Manitoba)
[PDF]

JUPITER ALGORTA, University of British Columbia
Exploring Cellular Polarization and Motility Through Bulk-Surface Dynamics  [PDF]

Cellular polarization and motility are fundamental processes in biology, underlying phenomena such as tissue development, immune response, and cancer metastasis. These behaviors are tightly regulated by proteins like GTPases, which act as molecular switches to control cellular protrusion. GTPases exhibit dynamic interplay between their active, membrane-bound form and inactive, cytoplasmic form, creating a spatially localized bistable system.

In this talk, I motivate a bulk-surface reaction-diffusion model that captures the coupling between cytoplasmic and membrane-bound GTPase dynamics, and connect it to an evolution law that deforms the domain in response to those dynamics. By integrating the biochemical processes governing GTPase activity with the physical deformation of the cell boundary, this framework provides a unified approach to studying how intracellular signaling drives cellular shape changes and motility.

RAQUEL BARREIRA, Polytechnic University of Setúbal
The evolving surface finite element method as a tool for solving PDEs on continuously evolving domains  [PDF]

In this talk we will demonstrate the capability, flexibility, versatility and generality of the evolving surface finite element method for solving partial differential systems on continuously evolving domains and surfaces with numerous applications in developmental biology, tumour growth and cell movement and deformation. Some applications will be presented, including on the numerical results of reaction-diffusion systems, with and without cross-diffusion, both on static and on evolving domains.

BRIAN CAMLEY, Johns Hopkins University
Controlling Cell Exploration and Oscillation Using Deposited Footprints  [PDF]

For eukaryotic cells to heal wounds, respond to immune signals, or metastasize, they must migrate, often by adhering to extracellular matrix. Cells may also deposit matrix, leaving behind a footprint that influences their crawling. Recent experiments showed that epithelial cells on micropatterned adhesive stripes move persistently in regions they have previously crawled on, where footprints have been formed, but barely advance into unexplored regions, creating an oscillatory migration of increasing amplitude. Here, we explore through mathematical modeling how footprint deposition and cell responses to footprint combine to allow cells to develop oscillation and other complex migratory motions. We simulate cell crawling with a phase field model coupled to a biochemical model of cell polarity, assuming local contact with the deposited footprint activates Rac1, a protein that establishes the cell's front. Depending on footprint deposition rate and response to the footprint, cells on micropatterned lines can display many types of motility, including confined, oscillatory, and persistent motion. On 2D substrates, we predict a transition between cells undergoing circular motion and cells developing an exploratory phenotype. Consistent with our computational predictions, we find in earlier experimental data evidence of cells undergoing both circular and exploratory motion.

DAVIDE CUSSEDDU, CMAT Centre of Mathematics, University of Minho
A bulk–surface modelling framework for cell polarisation  [PDF]

The bulk–surface wave–pinning model constitutes one of the simplest models of cell polarisation. It is a toy model that is derived from minimal key properties of GTPase proteins. In particular, the model takes into account the activation/inactivation dynamics as well as the spatial cycling of proteins between the cell membrane and the cytosol. In this talk I will present the model, some results and numerical simulations on different three–dimensional geometries.

CHUNYI GAI, University of Northern British Columbia
An Asymptotic Analysis of Spike Self-Replication and Spike Nucleation of Reaction-Diffusion Patterns on Growing 1-D Domains  [PDF]

Pattern formation on growing domains is one of the key issues in developmental biology, where domain growth has been shown to generate robust patterns under Turing instability. In this work, we investigate the mechanisms responsible for generating new spikes on a growing domain within the semi-strong interaction regime, focusing on three classical reaction-diffusion models: the Schnakenberg, Brusselator, and Gierer-Meinhardt (GM) systems. Our analysis identifies two distinct mechanisms of spike generation as the domain length increases. The first mechanism is spike self-replication, in which individual spikes split into two, effectively doubling the number of spikes. The second mechanism is spike nucleation, where new spikes emerge from a quiescent background via a saddle-node bifurcation of spike equilibria. Critical stability thresholds for these processes are derived, and global bifurcation diagrams are computed using the bifurcation software pde2path. These results yield a phase diagram in parameter space, outlining the distinct dynamical behaviors that can occur.

DAVID HOLLOWAY, British Columbia Institute of Technology
What makes cotyledon numbers so variable in conifers?  [PDF]

Flowering plants are characterized by having one (e.g. grasses) or two (e.g. broadleaf plants) embryonic leaves, or cotyledons. In contrast, conifer trees have a variable number of cotyledons, commonly ranging from 2 to 12 even in clonal cultures. What underlies this developmental freedom in number? I will present results using a hierarchical two-stage reaction-diffusion model to explore the pattern forming dynamics involved in forming the ringed arrangement of conifer cotyledons. This leads to a model of mutual inhibition between gene expression domains and the factors that can vary the cotyledon ring radius and produce the experimentally observed range of cotyledon number. The variability in conifer cotyledon ring size may have similarities to spatial scaling in fly embryos, in which gene expression pattern variation compensates for embryo length variability. The model provides a framework for quantitative experiments on the positional control of lateral organ initiation in embryos and mature plants. This could further understanding of the factors that control the leaf arrangements, or phyllotaxy, characteristic of plant species.

JACK HUGHES, University of British Columbia
Travelling waves and wave pinning (polarity): Switching between random and directional cell motility  [PDF]

We derive a simple model of actin waves consisting of three partial differential equations (PDEs) for active and inactive GTPase promoting growth of filamentous actin (F-actin, $F$). The F-actin feeds back to inactivate the GTPase at rate $sF$, where $s\ge 0$ is a "negative feedback" parameter. In contrast to previous models for actin waves, the simplicity of this model and its geometry (1D periodic cell perimeter) permits a local and global PDE bifurcation analysis. Based on a combination of continuation methods, linear stability analysis, and PDE simulations, we explore the existence, stability, interactions, and transitions between homogeneous steady states (resting cells), wave-pinning (polar cells), and travelling waves (cells with ruffling protrusions). We show that the value of $s$ and the size of the cell can affect the existence, coexistence, and stability of the patterns, as well as the dominance of one or another cell state. Implications to motile cells are discussed.

VICTOR JUMA, University of British Columbia
Diffusion-driven dynamics in bistable reaction-diffusion systems: Beyond Turing Instabilities  [PDF]

Bistability is a key feature in reaction-diffusion (RD) systems, enabling the coexistence of two stable equilibrium states and driving complex spatiotemporal behaviors; such as traveling waves, oscillatory pulses, and spatial patterns. While traditional analyses often focus on diffusion-driven instabilities (commonly known as Turing instability) arising from a uniform stable steady state, this study investigates the effect of diffusion on general steady states and limit cycles within a bistable reaction-diffusion system.

Using numerical simulations, we analyze how diffusion influences an ODE system exhibiting different dynamical behaviours; including stable steady state dynamics, bistable dynamics, limit cycle dynamics, and coexistence between uniform steady states and limit cycles.

In this talk, I will present a two-species reaction-diffusion model whose reaction kinetics are derived from first principles based on experimental observations. I will describe the model formulation and highlight key temporal dynamics of the model in the absence of diffusion. I will thereafter describe diffusion-driven transitions, such as spatial pattern formation and migration between steady states and migration of limit cycle in parameter regions far from classical Turing scenarios.

THEDORE KOLOKOLNIKOV, Dalhousie University
Stripe patterns for Gierer-Meinhard model in thin domains  [PDF]

We expore pattern formation for the GM model on thin domains. A motivating example is the development bone structure within the embryonic eye of birds. Experimental evidence to-date points to a Turing mechanism of pattern formation on thin domains.

If the domain is sufficiently thin, the pattern consists of stripes which are nearly one-dimensional. We analyse patterns consisting of one, two or many stripes. We find that a single stripe can be located either at the thickest or thinnest part of the channel, depending on the choice of parameters. In the limit of many stripes, we derive an effective pattern density description of the equilibrium state. The effective density is easily computable as a solution of a first order ODE subject to an integral constraint. Depending on problem parameters, the resulting pattern can be either global spanning the entire domain, or can be clustered near either thickest or thinnest part of the domain. In addition, instability thresholds are derived from the continuum density limit of many stripes. Full two-dimensional numerical simulations are performed and are shown to be in agreement with the asymptotic results. Results are shown to be applicable to

KUDZANAYI MAPFUMO, University of British Columbia
The spatiotemporal dynamics of Rho-GEF-H1-Myosin reaction-diffusion system  [PDF]

In this presentation, I explore the spatiotemporal dynamics of the Rho-GEF-H1-Myosin signaling network through a reaction-diffusion model. I analyze temporal and spatial behaviors to uncover how feedback mechanisms and diffusion influence the system dynamics. By performing bifurcation and phase plane analyses, I identify stable, oscillatory, and bistable regimes. Numerical simulations reveal how spatial variations influence dynamic behaviors in these regimes, including providing insights into pattern formation.

PEARSON W. MILLER, University of California, San Diego
Geometric effects in bulk-surface dynamics  [PDF]

Reaction-diffusion equations with nonlocal constraints naturally arise as limiting cases of mathematical models of intracellular signaling. Among the interesting behaviors of these models, much has been made of their 'geometry-sensing' properties: the strong sensitivity of steady-state solutions to domain geometry is widely seen as illustrative of how a cell establishes an internal coordinate axis. In this talk, I describe recent efforts to formally clarify this geometry dependence through careful study of the long-time behavior of a popular model of biochemical symmetry breaking. Using the tools of formal asymptotics, calculus of variations, and a new fast solver for surface-bound PDEs, we study the formation and motion of interfaces on a curved domain across three dynamical timescales. Our results allow us to construct several analytical steady-state solutions that serve as counter-examples to received wisdom regarding the geometry-dependence of this class of model.

ALI FELE PARANJ, UBC
Generation and Evolution of Vascular Netowrks  [PDF]

Vascular networks are hierarchical structures essential for delivering oxygen and nutrients to tissues while removing waste from the body. The initial microvasculature plexus has no hierarchical organization. This immature network, characterized by high hydrodynamic energy dissipation, is inefficient for fulfilling the functions of a mature vascular network. We used a Branching Annihilating Random Walk process to generate the initial microvascular plexus and investigate the mechanisms by which this premature network evolves into a mature, and hierarchical system.

MERLIN PELZ, University of Minnesota, Twin Cities
Symmetry-Breaking in Compartmental-Reaction Diffusion Systems with Comparable Diffusivities  [PDF]

Since Alan Turing’s pioneering publication on morphogenetic pattern formation obtained with reaction-diffusion (RD) systems, it has been the prevailing belief that two-component reaction diffusion systems have to include a fast diffusing inhibiting component (inhibitor) and a much slower diffusing activating component (activator) in order to break symmetry from a uniform steady-state. This time-scale separation is often unbiological for cell signal transduction pathways. We modify the traditional RD paradigm by considering nonlinear reaction kinetics only inside compartments (cells) with reactive boundary conditions to the extra-compartmental space which diffusively couples the compartments via two (chemical) species. The construction of a nonlinear algebraic system for all existing steady-states, or quasi-steady-states, enables us to derive a globally coupled matrix eigenvalue problem for the growth rates of eigenperturbations from the symmetric steady-state in 1-D, 2-D, and 3-D. We show that the membrane reaction rate ratio of inhibitor rate to activator rate is a key bifurcation parameter leading to robust symmetry-breaking of the compartments. Illustrated with Gierer-Meinhardt, FitzHugh-Nagumo and Rauch-Millonas intra-compartmental kinetics, our compartmental-reaction diffusion system does not require diffusion of inhibitor and activator on vastly different time scales. Our results reveal a possible simple mechanism of the ubiquitous biological steady and oscillatory cell specialization observed in nature. (This is joint work with Michael J. Ward.)

STEVEN RUUTH, Simon Fraser University
A Closest Point Method for PDEs on Manifolds with Interior Boundary Conditions for Geometry Processing  [PDF]

Solving partial differential equations (PDEs) on manifolds is fundamental to many geometry processing tasks, such as diffusion curves on surfaces, geodesic computations, tangent vector field design, and reaction-diffusion textures. These PDEs often involve boundary conditions prescribed at points or curves on the manifold’s interior or along the geometric boundary of an open manifold.

We present a robust extension of the closest point method (CPM) for handling interior boundary conditions. The CPM reformulates the manifold PDE as a volumetric PDE in the Cartesian embedding space, requiring only the closest point representation of the manifold. This approach inherently supports open or closed manifolds, orientable or not, and of any codimension. To address interior boundary conditions, we derive a technique that implicitly partitions the embedding space across interior boundaries, modifying finite difference and interpolation stencils to respect these partitions while preserving second-order accuracy.

Our method includes an efficient sparse-grid implementation and scalable numerical solver capable of handling tens of millions of degrees of freedom, enabling solutions on complex manifolds. We demonstrate the convergence and accuracy of our approach using model PDEs and showcase applications to a range of geometry processing problems.

This is joint work with Nathan King (University of Waterloo), Haozhe Su (Lightspeed Studios), Mridul Aanjaneya (Rutgers University), and Christopher Batty (University of Waterloo).

CLEMENT SOUBRIER, UBC
Experimental analysis of M. smegmatis morphological feature dynamics and modelling using reaction-diffusion systems.  [PDF]

Atomic Force Microscopy (AFM) is a quantitative scanning technology capturing cell surface mechanical properties such as height, chemical adhesion or stiffness. Recent advances in coupling AFM-based nanoscale spatial resolution with temporal data has allowed to observe the dynamics of cellular morphology at an unprecedented scale, and study key cellular mechanisms over long time range. \newline

In this talk, we analyze experimental data to investigate Mycobacterium smegmatis morphology over time, and model pattern dynamics using a reaction-diffusion system. This non pathogenic and fast growing bacterium is commonly studied as a model for harmful mycobacteria such as M. tuberculosis, since they share a similar cell wall structure. Upon using our pipeline to reduce the cell surface geometry to its center-line and measure height variation along it, we confirm the presence of peaks and troughs on the cell surface, as consistent features of the morphology. We also show how these features relate to bi-phasic and asymmetric polar growth dynamics, as well as division site selection. Finally, we show that a minimal reaction-diffusion model on a growing domain can reproduce and maintain similar feature over time, enabling a better understanding of yet unknown morphology controlling pathways.

FABIAN SPILL, University of Birmingham
Cellular and Subcellular Geometry and Mechanics as Determinants of Cell Migration  [PDF]

The migration of epithelial cells plays a critical role in physiological processes such as wound healing. In this context, cells utilize distinct migration modes based on the geometric properties of gaps: lamellipodial crawling at convex edges and purse-string-like movements at concave edges. Despite advances in identifying biochemical pathways, the underlying mechanisms determining these mode switches in response to curvature remain unclear. Our study addresses this by focusing on the endoplasmic reticulum (ER), a dynamic organelle whose morphology depends on cellular geometry. Through a combination of experimental data and theoretical modeling, we show that the ER undergoes curvature-specific morphological reorganizations that act as a determinant of migration modes. At convex edges, the ER forms tubular networks that align perpendicularly, facilitating lamellipodial crawling. At concave edges, the ER reorganizes into dense sheet-like structures favoring actomyosin-driven purse-string contractions. Our mathematical model describes the ER as a flexible fiber whose morphology-dependent strain energy guides these transitions, revealing a lower energy state when ER tubules or sheets form in accordance with local edge curvature. This study positions the ER as a critical player in cellular mechanotransduction, providing a mechanistic link between subcellular organization and cellular migration strategies. Our findings offer insights into how cellular and subcellular geometries dynamically influence the physical properties and behaviors of cells, forming a basis for understanding migration regulation in complex tissues.

MICHAEL WARD, UBC
Pattern Forming Systems Coupling Linear Bulk Diffusion to Dynamically Active Membranes or Cells  [PDF]

Some analytical and numerical results are presented for pattern formation properties associated with novel types of reaction-diffusion (RD) systems that involve the coupling of bulk diffusion in the interior of a multi-dimensional spatial domain to nonlinear processes that occur either on the domain boundary or within localized compartments that are confined within the domain. The class of bulk-membrane system considered herein is derived from an asymptotic analysis in the limit of small thickness of a thin domain that surrounds the bulk medium. When the bulk domain is a 2-D disk, a weakly nonlinear analysis is used to characterize Turing and Hopf bifurcations that can arise from the linearization around a radially symmetric, but spatially non-uniform, steady-state of the bulk-membrane system. Some results in 1-D coupling bulk diffusion to dynamically active compartments with chaotic dynamics are also discussed. Finally, the emergence of collective intracellular oscillations is studied for a class of PDE-ODE bulk-cell model that involves spatially localized, but dynamically active, cells that are coupled through a linear bulk diffusion field. Applications of such coupled bulk-membrane or bulk-cell systems to some biological systems are outlined, and some open problems are discussed. Joint work with Frederic Paquin-Lefebvre, Sarafa Iyaniwura, Wayne Nagata, and Merlin Pelz

FENGWEI YANG, University of British Columbia
Combining image analysis and cell migration model for whole cell tracking  [PDF]

Cell tracking algorithms which automate and systematise the analysis of time-lapse image data sets of cells are an indispensable tool in the modelling and understanding cellular phenomena. we present a theoretical framework and an algorithm for whole-cell tracking. Within this work, we consider that “tracking” is equivalent to a dynamic reconstruction of the whole cell data (morphologies) from static image data sets. This work aims to design a framework for cell tracking within which the recovered data reflects the physics of the forward model.


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