Bridging from single to collective cell migration: A review of models and links to experiments

Mathematical and computational models can assist in gaining an understanding of cell behavior at many levels of organization. Here, we review models in the literature that focus on eukaryotic cell motility at 3 size scales: intracellular signaling that regulates cell shape and movement, single cell motility, and collective cell behavior from a few cells to tissues. We survey recent literature to summarize distinct computational methods (phase-field, polygonal, Cellular Potts, and spherical cells). We discuss models that bridge between levels of organization, and describe levels of detail, both biochemical and geometric, included in the models. We also highlight links between models and experiments. We find that models that span the 3 levels are still in the minority.Comment: 39 pages, 5 figure

Boundary-driven instability

We analyse a reaction-diffusion system and show that complex spatial patterns can be generated by imposing Dirichlet boundary conditions on one or more of the reactant concentrations. This pattern persists even when the homogeneous steady state with Neumann conditions is stable

A coupled bulk-surface model for cell polarisation

Several cellular activities, such as directed cell migration, are coordinated by an intricate network of biochemical reactions which lead to a polarised state of the cell, in which cellular symmetry is broken, causing the cell to have a well defined front and back. Recent work on balancing biological complexity with mathematical tractability resulted in the proposal and formulation of a famous minimal model for cell polarisation, known as the wave pinning model. In this study, we present a three-dimensional generalisation of this mathematical framework through the maturing theory of coupled bulk-surface semilinear partial differential equations in which protein compartmentalisation becomes natural. We show how a local perturbation over the surface can trigger propagating reactions, eventually stopped in a stable profile by the interplay with the bulk component. We describe the behaviour of the model through asymptotic and local perturbation analysis, in which the role of the geometry is investigated. The bulk-surface finite element method is used to generate numerical simulations over simple and complex geometries, which confirm our analysis, showing pattern formation due to propagation and pinning dynamics. The generality of our mathematical and computational framework allows to study more complex biochemical reactions and biomechanical properties associated with cell polarisation in multi-dimensions

Adaptive Pseudo-Transient-Continuation-Galerkin Methods for Semilinear Elliptic Partial Differential Equations

In this paper we investigate the application of pseudo-transient-continuation (PTC) schemes for the numerical solution of semilinear elliptic partial differential equations, with possible singular perturbations. We will outline a residual reduction analysis within the framework of general Hilbert spaces, and, subsequently, employ the PTC-methodology in the context of finite element discretizations of semilinear boundary value problems. Our approach combines both a prediction-type PTC-method (for infinite dimensional problems) and an adaptive finite element discretization (based on a robust a posteriori residual analysis), thereby leading to a fully adaptive PTC-Galerkin scheme. Numerical experiments underline the robustness and reliability of the proposed approach for different examples.Comment: arXiv admin note: text overlap with arXiv:1408.522

Locust Dynamics: Behavioral Phase Change and Swarming

Locusts exhibit two interconvertible behavioral phases, solitarious and gregarious. While solitarious individuals are repelled from other locusts, gregarious insects are attracted to conspecifics and can form large aggregations such as marching hopper bands. Numerous biological experiments at the individual level have shown how crowding biases conversion towards the gregarious form. To understand the formation of marching locust hopper bands, we study phase change at the collective level, and in a quantitative framework. Specifically, we construct a partial integrodifferential equation model incorporating the interplay between phase change and spatial movement at the individual level in order to predict the dynamics of hopper band formation at the population level. Stability analysis of our model reveals conditions for an outbreak, characterized by a large scale transition to the gregarious phase. A model reduction enables quantification of the temporal dynamics of each phase, of the proportion of the population that will eventually gregarize, and of the time scale for this to occur. Numerical simulations provide descriptions of the aggregation's structure and reveal transiently traveling clumps of gregarious insects. Our predictions of aggregation and mass gregarization suggest several possible future biological experiments.Comment: Main text plus figures and supporting information; to appear in PLOS Computational Biolog

Dynamic coordinated control laws in multiple agent models

We present an active control scheme of a kinetic model of swarming. It has been shown previously that the global control scheme for the model, presented in \cite{JK04}, gives rise to spontaneous collective organization of agents into a unified coherent swarm, via a long-range attractive and short-range repulsive potential. We extend these results by presenting control laws whereby a single swarm is broken into independently functioning subswarm clusters. The transition between one coordinated swarm and multiple clustered subswarms is managed simply with a homotopy parameter. Additionally, we present as an alternate formulation, a local control law for the same model, which implements dynamic barrier avoidance behavior, and in which swarm coherence emerges spontaneously.Comment: 20 pages, 6 figure