Realizing the physics of motile cilia synchronization with driven colloids

Cilia and flagella in biological systems often show large scale cooperative behaviors such as the synchronization of their beats in "metachronal waves". These are beautiful examples of emergent dynamics in biology, and are essential for life, allowing diverse processes from the motility of eukaryotic microorganisms, to nutrient transport and clearance of pathogens from mammalian airways. How these collective states arise is not fully understood, but it is clear that individual cilia interact mechanically,and that a strong and long ranged component of the coupling is mediated by the viscous fluid. We review here the work by ourselves and others aimed at understanding the behavior of hydrodynamically coupled systems, and particularly a set of results that have been obtained both experimentally and theoretically by studying actively driven colloidal systems. In these controlled scenarios, it is possible to selectively test aspects of the living motile cilia, such as the geometrical arrangement, the effects of the driving profile and the distance to no-slip boundaries. We outline and give examples of how it is possible to link model systems to observations on living systems, which can be made on microorganisms, on cell cultures or on tissue sections. This area of research has clear clinical application in the long term, as severe pathologies are associated with compromised cilia function in humans.Comment: 31 pages, to appear in Annual Review of Condensed Matter Physic

A stable and accurate control-volume technique based on integrated radial basis function networks for fluid-flow problems

Radial basis function networks (RBFNs) have been widely used in solving partial differential equations as they are able to provide fast convergence. Integrated RBFNs have the ability to avoid the problem of reduced convergence-rate caused by differentiation. This paper is concerned with the use of integrated RBFNs in the context of control-volume discretisations for the simulation of fluid-flow problems. Special attention is given to (i) the development of a stable high-order upwind scheme for the convection term and (ii) the development of a local high-order approximation scheme for the diffusion term. Benchmark problems including the lid-driven triangular-cavity flow are employed to validate the present technique. Accurate results at high values of the Reynolds number are obtained using relatively-coarse grids

Non-linear modeling of active biohybrid materials

Recent advances in engineered muscle tissue attached to a synthetic substrate motivates the development of appropriate constitutive and numerical models. Applications of active materials can be expanded by using robust, non-mammalian muscle cells, such as those of Manduca sexta. In this study, we propose a model to assist in the analysis of biohybrid constructs by generalizing a recently proposed constitutive law for Manduca muscle tissue. The continuum model accounts (i) for the stimulation of muscle fibers by introducing multiple stress-free reference configurations for the active and passive states and (ii) for the hysteretic response by specifying a pseudo-elastic energy function. A simple example representing uniaxial loading-unloading is used to validate and verify the characteristics of the model. Then, based on experimental data of muscular thin films, a more complex case shows the qualitative potential of Manduca muscle tissue in active biohybrid constructs

Particle methods for a virtual patient

The particle systems approach is a well known technique in computer graphics for modelling fuzzy objects such as fire and clouds. The algorithm has also been applied to different biomedical applications and this paper presents two such methods: a charged particle method for soft tissue deformation with integrated haptics; and a blood flow visualization technique based on boids. The goal is real time performance with high fidelity results

Structural characterization and statistical-mechanical model of epidermal patterns

In proliferating epithelia of mammalian skin, cells of irregular polygonal-like shapes pack into complex nearly flat two-dimensional structures that are pliable to deformations. In this work, we employ various sensitive correlation functions to quantitatively characterize structural features of evolving packings of epithelial cells across length scales in mouse skin. We find that the pair statistics in direct and Fourier spaces of the cell centroids in the early stages of embryonic development show structural directional dependence, while in the late stages the patterns tend towards statistically isotropic states. We construct a minimalist four-component statistical-mechanical model involving effective isotropic pair interactions consisting of hard-core repulsion and extra short-ranged soft-core repulsion beyond the hard core, whose length scale is roughly the same as the hard core. The model parameters are optimized to match the sample pair statistics in both direct and Fourier spaces. By doing this, the parameters are biologically constrained. Our model predicts essentially the same polygonal shape distribution and size disparity of cells found in experiments as measured by Voronoi statistics. Moreover, our simulated equilibrium liquid-like configurations are able to match other nontrivial unconstrained statistics, which is a testament to the power and novelty of the model. We discuss ways in which our model might be extended so as to better understand morphogenesis (in particular the emergence of planar cell polarity), wound-healing, and disease progression processes in skin, and how it could be applied to the design of synthetic tissues

A novel model for one-dimensional morphoelasticity. Part I - Theoretical foundations

While classical continuum theories of elasticity and viscoelasticity have long been used to describe the mechanical behaviour of solid biological tissues, they are of limited use for the description of biological tissues that undergo continuous remodelling. The structural changes to a soft tissue associated with growth and remodelling require a mathematical theory of ‘morphoelasticity’ that is more akin to plasticity than elasticity. However, previously-derived mathematical models for plasticity are difficult to apply and interpret in the context of growth and remodelling: many important concepts from the theory of plasticity do not have simple analogues in biomechanics.\ud \ud In this work, we describe a novel mathematical model that combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. While our focus here is on one-dimensional problems, our model builds on earlier work based on the multiplicative decomposition of the deformation gradient and can be adapted to develop a three-dimensional theory. The foundation of this work is the concept of ‘effective strain’, a measure of the difference between the current state and a hypothetical state where the tissue is mechanically relaxed. We develop one-dimensional equations for the evolution of effective strain, and discuss a number of potential applications of this theory. One significant application is the description of a contracting fibroblast-populated collagen lattice, which we further investigate in Part II