Non-local impact of distal airway constrictions on patterns of inhaled particle deposition.

Airway constriction and blockage in obstructive lung diseases cause ventilation heterogeneity and create barriers to effective drug deposition. Established computational particle-deposition models have not accounted for these impacts of disease. We present a new particle-deposition model that calculates ventilation based on the resistance of each airway, such that ventilation responds to airway constriction.

Relaxation and Noise-Driven Oscillations in a Model of Mitotic Spindle Dynamics.

During cell division, the mitotic spindle moves dynamically through the cell to position the chromosomes and determine the ultimate spatial position of the two daughter cells. These movements have been attributed to the action of cortical force generators which pull on the astral microtubules to position the spindle, as well as pushing events by these same microtubules against the cell cortex and plasma membrane. Attachment and detachment of cortical force generators working antagonistically against centring forces of microtubules have been modelled previously (Grill et al.

Surfactant amplifies yield-stress effects in the capillary instability of a film coating a tube.

To assess how the presence of surfactant in lung airways alters the flow of mucus that leads to plug formation and airway closure, we investigate the effect of insoluble surfactant on the instability of a viscoplastic liquid coating the interior of a cylindrical tube. Evolution equations for the layer thickness using thin-film and long-wave approximations are derived that incorporate yield-stress effects and capillary and Marangoni forces. Using numerical simulations and asymptotic analysis of the thin-film system, we quantify how the presence of surfactant slows growth of the Rayleigh-Plateau instability, increases the size of initial perturbation required to trigger instability and decreases the final peak height of the layer.

Investigation of Performance Parameters of Spherical Gold Nanoparticles in Localized Surface Plasmon Resonance Biosensing.

In this paper, we present numerical and experimental results on Localized Surface Plasmon Resonance (LSPR) refractive index (RI) sensitivity, Figure of Merit (FoM), and penetration depth () dependence on spherical gold nanoparticles (AuNPs) size, and the effects of AuNP dimer interparticle distance () studied numerically. These parameters were calculated and observed for = 20, 40, 60, 80, and 100 nm diameter spherical AuNPs. Our investigation shows = 60 nm AuNPs give the best FoM.

Modeling collagen fibril self-assembly from extracellular medium in embryonic tendon.

Collagen is a key structural component of multicellular organisms and is arranged in a highly organized manner. In structural tissues such as tendons, collagen forms bundles of parallel fibers between cells, which appear within a 24-h window between embryonic day 13.5 (E13.

Red blood cell dynamics in extravascular biological tissues modelled as canonical disordered porous media.

The dynamics of blood flow in the smallest vessels and passages of the human body, where the cellular character of blood becomes prominent, plays a dominant role in the transport and exchange of solutes. Recent studies have revealed that the microhaemodynamics of a vascular network is underpinned by its interconnected structure, and certain structural alterations such as capillary dilation and blockage can substantially change blood flow patterns. However, for extravascular media with disordered microstructure (e.

Couple stresses and discrete potentials in the vertex model of cellular monolayers.

The vertex model is widely used to simulate the mechanical properties of confluent epithelia and other multicellular tissues. This inherently discrete framework allows a Cauchy stress to be attributed to each cell, and its symmetric component has been widely reported, at least for planar monolayers. Here, we consider the stress attributed to the neighbourhood of each tricellular junction, evaluating in particular its leading-order antisymmetric component and the associated couple stresses, which characterise the degree to which individual cells experience (and resist) in-plane bending deformations.

Advection-dominated transport past isolated disordered sinks: stepping beyond homogenization.

We investigate the transport of a solute past isolated sinks in a bounded domain when advection is dominant over diffusion, evaluating the effectiveness of homogenization approximations when sinks are distributed uniformly randomly in space. Corrections to such approximations can be non-local, non-smooth and non-Gaussian, depending on the physical parameters (a Péclet number Pe, assumed large, and a Damköhler number Da) and the compactness of the sinks. In one spatial dimension, solute distributions develop a staircase structure for large , with corrections being better described with credible intervals than with traditional moments.

Model-based Bayesian inference of the ventilation distribution in patients with cystic fibrosis from multiple breath washout, with comparison to ventilation MRI.

Background: Indices of ventilation heterogeneity (VH) from multiple breath washout (MBW) have been shown to correlate well with VH indices derived from hyperpolarised gas ventilation MRI. Here we report the prediction of ventilation distributions from MBW data using a mathematical model, and the comparison of these predictions with imaging data.

Methods: We developed computer simulations of the ventilation distribution in the lungs to model MBW measurement with 3 parameters: σ determining the extent of VH; V, the lung volume; and V, the dead-space volume.

Collagen fibril assembly: New approaches to unanswered questions.

Collagen fibrils are essential for metazoan life. They are the largest, most abundant, and most versatile protein polymers in animals, where they occur in the extracellular matrix to form the structural basis of tissues and organs. Collagen fibrils were first observed at the turn of the 20th century.

Force networks, torque balance and Airy stress in the planar vertex model of a confluent epithelium.

The vertex model is a popular framework for modelling tightly packed biological cells, such as confluent epithelia. Cells are described by convex polygons tiling the plane and their equilibrium is found by minimizing a global mechanical energy, with vertex locations treated as degrees of freedom. Drawing on analogies with granular materials, we describe the force network for a localized monolayer and derive the corresponding discrete Airy stress function, expressed for each -sided cell as scalars defined over kites covering the cell.

Quantifying the impact of tissue metabolism on solute transport in feto-placental microvascular networks.

The primary exchange units in the human placenta are terminal villi, in which fetal capillary networks are surrounded by a thin layer of villous tissue, separating fetal from maternal blood. To understand how the complex spatial structure of villi influences their function, we use an image-based theoretical model to study the effect of tissue metabolism on the transport of solutes from maternal blood into the fetal circulation. For solute that is taken up under first-order kinetics, we show that the transition between flow-limited and diffusion-limited transport depends on two new dimensionless parameters defined in terms of key geometric quantities, with strong solute uptake promoting flow-limited transport conditions.

Physical and geometric determinants of transport in fetoplacental microvascular networks.

Across mammalian species, solute exchange takes place in complex microvascular networks. In the human placenta, the primary exchange units are terminal villi that contain disordered networks of fetal capillaries and are surrounded externally by maternal blood. We show how the irregular internal structure of a terminal villus determines its exchange capacity for diverse solutes.

Decoupling the Roles of Cell Shape and Mechanical Stress in Orienting and Cueing Epithelial Mitosis.

Distinct mechanisms involving cell shape and mechanical force are known to influence the rate and orientation of division in cultured cells. However, uncoupling the impact of shape and force in tissues remains challenging. Combining stretching of Xenopus tissue with mathematical methods of inferring relative mechanical stress, we find separate roles for cell shape and mechanical stress in orienting and cueing division.

Modelling structural determinants of ventilation heterogeneity: A perturbative approach.

We have developed a computational model of gas mixing and ventilation in the human lung represented as a bifurcating network. We have simulated multiple-breath washout (MBW), a clinical test for measuring ventilation heterogeneity (VH) in patients with obstructive lung conditions. By applying airway constrictions inter-regionally, we have predicted the response of MBW indices to obstructions and found that they detect a narrow range of severe constrictions that reduce airway radius to 10%-30% of healthy values.

Effect of intermittent inspiratory leaks on measurement of lung clearance index using nitrogen and sulfur hexafluoride.

http://ow.ly/az7b30lG5Ku.

A Mechanosensitive RhoA Pathway that Protects Epithelia against Acute Tensile Stress.

Adherens junctions are tensile structures that couple epithelial cells together. Junctional tension can arise from cell-intrinsic application of contractility or from the cell-extrinsic forces of tissue movement. Here, we report a mechanosensitive signaling pathway that activates RhoA at adherens junctions to preserve epithelial integrity in response to acute tensile stress.

Curvature-Sensitive Kinesin Binding Can Explain Microtubule Ring Formation and Reveals Chaotic Dynamics in a Mathematical Model.

Microtubules are filamentous tubular protein polymers which are essential for a range of cellular behaviour, and are generally straight over micron length scales. However, in some gliding assays, where microtubules move over a carpet of molecular motors, individual microtubules can also form tight arcs or rings, even in the absence of crosslinking proteins. Understanding this phenomenon may provide important explanations for similar highly curved microtubules which can be found in nerve cells undergoing neurodegeneration.

Osmotic and electroosmotic fluid transport across the retinal pigment epithelium: A mathematical model.

The retinal pigment epithelium (RPE) is the outermost cell layer of the retina. It has several important physiological functions, among which is removal of excess fluid from the sub-retinal space by pumping it isotonically towards the choroid. Failure of this pumping leads to fluid accumulation, which is closely associated with several pathological conditions, such as age-related macular degeneration, macular oedema and retinal detachment.

Mechanical characterization of disordered and anisotropic cellular monolayers.

We consider a cellular monolayer, described using a vertex-based model, for which cells form a spatially disordered array of convex polygons that tile the plane. Equilibrium cell configurations are assumed to minimize a global energy defined in terms of cell areas and perimeters; energy is dissipated via dynamic area and length changes, as well as cell neighbor exchanges. The model captures our observations of an epithelium from a Xenopus embryo showing that uniaxial stretching induces spatial ordering, with cells under net tension (compression) tending to align with (against) the direction of stretch, but with the stress remaining heterogeneous at the single-cell level.

Three-dimensional plant architecture and sunlit-shaded patterns: a stochastic model of light dynamics in canopies.

Background And Aims: Diurnal changes in solar position and intensity combined with the structural complexity of plant architecture result in highly variable and dynamic light patterns within the plant canopy. This affects productivity through the complex ways that photosynthesis responds to changes in light intensity. Current methods to characterize light dynamics, such as ray-tracing, are able to produce data with excellent spatio-temporal resolution but are computationally intensive and the resulting data are complex and high-dimensional.