Modelling pulsatile blood flow through surgically coupled microvascular anastomoses

The significant rates of post-operative arterial thrombus formation following the sutured anastomosis (surgical connection) of vessels in microvascular reconstruction has kindled the development of engineered solutions such as the UNILINK coupler. These devices reduce thrombosis rates, which recent numerical studies suggest to be due to decreases in shear strain rate across the anastomosis site when compared to sutured vessels. In this work we develop and analytically solve the first mathematical model for the problem of microvascular anastomosis, leading to the discovery that the rates of thrombosis using these surgical coupling devices could be further reduced by decreasing the gradient of the wall deformation at the join.Comment: 8 pages, 3 figure

Sharp quadrature error bounds for the nearest-neighbor discretization of the regularized stokeslet boundary integral equation

The method of regularized stokeslets is a powerful numerical method to solve the Stokes flow equations for problems in biological fluid mechanics. A recent variation of this method incorporates a nearest-neighbor discretization to improve accuracy and efficiency while maintaining the ease-of-implementation of the original meshless method. This method contains three sources of numerical error, the regularization error associated from using the regularized form of the boundary integral equations (with parameter $\varepsilon$), and two sources of discretization error associated with the force and quadrature discretizations (with lengthscales $h_f$ and $h_q$). A key issue to address is the quadrature error: initial work has not fully explained observed numerical convergence phenomena. In the present manuscript we construct sharp quadrature error bounds for the nearest-neighbor discretisation, noting that the error for a single evaluation of the kernel depends on the smallest distance ($\delta$) between these discretization sets. The quadrature error bounds are described for two cases: with disjoint sets ($\delta>0$) being close to linear in $h_q$ and insensitive to $\varepsilon$, and contained sets ($\delta=0$) being quadratic in $h_q$ with inverse dependence on $\varepsilon$. The practical implications of these error bounds are discussed with reference to the condition number of the matrix system for the nearest-neighbor method, with the analysis revealing that the condition number is insensitive to $\varepsilon$ for disjoint sets, and grows linearly with $\varepsilon$ for contained sets. Error bounds for the general case ($\delta\geq 0$) are revealed to be proportional to the sum of the errors for each case.Comment: 12 pages, 6 figure

Passively parallel regularized stokeslets

Stokes flow, discussed by G.G. Stokes in 1851, describes many microscopic biological flow phenomena, including cilia-driven transport and flagellar motility; the need to quantify and understand these flows has motivated decades of mathematical and computational research. Regularized stokeslet methods, which have been used and refined over the past twenty years, offer significant advantages in simplicity of implementation, with a recent modification based on nearest-neighbour interpolation providing significant improvements in efficiency and accuracy. Moreover this method can be implemented with the majority of the computation taking place through built-in linear algebra, entailing that state-of-the-art hardware and software developments in the latter, in particular multicore and GPU computing, can be exploited through minimal modifications ('passive parallelism') to existing MATLAB computer code. Hence, and with widely-available GPU hardware, significant improvements in the efficiency of the regularized stokeslet method can be obtained. The approach is demonstrated through computational experiments on three model biological flows: undulatory propulsion of multiple C. Elegans, simulation of progression and transport by multiple sperm in a geometrically confined region, and left-right symmetry breaking particle transport in the ventral node of the mouse embryo. In general an order-of-magnitude improvement in efficiency is observed. This development further widens the complexity of biological flow systems that are accessible without the need for extensive code development or specialist facilities.Comment: 21 pages, 7 figures, submitte

Beta cell lipotoxicity in the development of type 2 diabetes:the need for species-specific understanding

The propensity to develop type 2 diabetes (T2D) is known to have both environmental and hereditary components. In those with a genetic predisposition to T2D, it is widely believed that elevated concentrations of circulatory long-chain fatty acids (LC-FFA) significantly contribute towards the demise of insulin-producing pancreatic β-cells - the fundamental feature of the development of T2D. Over 25 years of research support that LC-FFA are deleterious to β-cells, through a process termed lipotoxicity. However, the work underpinning the theory of β-cell lipotoxicity is mostly based on rodent studies. Doubts have been raised as to whether lipotoxicity also occurs in humans. In this review, we examine the evidence, both in vivo and in vitro, for the pathogenic effects of LC-FFA on β-cell viability and function in humans, highlighting key species differences. In this way, we aim to uncover the role of lipotoxicity in the human pathogenesis of T2D and motivate the need for species-specific understanding.</p

Efficient Implementation of Elastohydrodynamics via Integral Operators

The dynamics of geometrically non-linear flexible filaments play an important role in a host of biological processes, from flagella-driven cell transport to the polymeric structure of complex fluids. Such problems have historically been computationally expensive due to numerical stiffness associated with the inextensibility constraint, as well as the often non-trivial boundary conditions on the governing high-order PDEs. Formulating the problem for the evolving shape of a filament via an integral equation in the tangent angle has recently been found to greatly alleviate this numerical stiffness. The contribution of the present manuscript is to enable the simulation of non-local interactions of multiple filaments in a computationally efficient manner using the method of regularized stokeslets within this framework. The proposed method is benchmarked against a non-local bead and link model, and recent code utilizing a local drag velocity law. Systems of multiple filaments (1) in a background fluid flow, (2) under a constant body force, and (3) undergoing active self-motility are modeled efficiently. Buckling instabilities are analyzed by examining the evolving filament curvature, as well as by coarse-graining the body frame tangent angles using a Chebyshev approximation for various choices of the relevant non-dimensional parameters. From these experiments, insight is gained into how filament-filament interactions can promote buckling, and further reveal the complex fluid dynamics resulting from arrays of these interacting fibers. By examining active moment-driven filaments, we investigate the speed of worm- and sperm-like swimmers for different governing parameters. The MATLAB(R) implementation is made available as an open-source library, enabling flexible extension for alternate discretizations and different surrounding flows.Comment: 37 pages, 17 figure

Doing more with less: the flagellar end piece enhances the propulsive effectiveness of human spermatozoa

Spermatozoa self-propel by propagating bending waves along a predominantly active elastic flagellum. The organized structure of the "9 + 2" axoneme is lost in the most-distal few microns of the flagellum, and therefore this region is unlikely to have the ability to generate active bending; as such it has been largely neglected in biophysical studies. Through elastohydrodynamic modeling of human-like sperm we show that an inactive distal region confers significant advantages, both in propulsive thrust and swimming efficiency, when compared with a fully active flagellum of the same total length. The beneficial effect of the inactive end piece on these statistics can be as small as a few percent but can be above 430%. The optimal inactive length, between 2-18% of the total length, depends on both wavenumber and viscous-elastic ratio, and therefore is likely to vary in different species. Potential implications in evolutionary biology and clinical assessment are discussed.Comment: To Appear, Physical Review Fluids. 25 pages, 14 figure