Computational Biorheology of Human Blood Flow in Health and Disease

Abstract

Hematologic disorders arising from infectious diseases, hereditary factors and environmental influences can lead to, and can be influenced by, significant changes in the shape, mechanical and physical properties of red blood cells (RBCs), and the biorheology of blood flow. Hence, modeling of hematologic disorders should take into account the multiphase nature of blood flow, especially in arterioles and capillaries. We present here an overview of a general computational framework based on dissipative particle dynamics (DPD) which has broad applicability in cell biophysics with implications for diagnostics, therapeutics and drug efficacy assessments for a wide variety of human diseases. This computational approach, validated by independent experimental results, is capable of modeling the biorheology of whole blood and its individual components during blood flow so as to investigate cell mechanistic processes in health and disease. DPD is a Lagrangian method that can be derived from systematic coarse-graining of molecular dynamics but can scale efficiently up to arterioles and can also be used to model RBCs down to the spectrin level. We start from experimental measurements of a single RBC to extract the relevant biophysical parameters, using single-cell measurements involving such methods as optical tweezers, atomic force microscopy and micropipette aspiration, and cell-population experiments involving microfluidic devices. We then use these validated RBC models to predict the biorheological behavior of whole blood in healthy or pathological states, and compare the simulations with experimental results involving apparent viscosity and other relevant parameters. While the approach discussed here is sufficiently general to address a broad spectrum of hematologic disorders including certain types of cancer, this paper specifically deals with results obtained using this computational framework for blood flow in malaria and sickle cell anemia.

Multiscale Particle-Based Modeling of Flowing Platelets in Blood Plasma Using Dissipative Particle Dynamics and Coarse Grained Molecular Dynamics

“…The mesoscopic particle-based methods are recently developed to model the blood cells and the thrombosis. For example, the discrete particle dynamics algorithms are widely used for modeling the surrounding fluids 16,20 , the blood flows in microvessel 15 , the interactions of blood cells 23 and the thrombosis growth 22,67 . However, the platelets are still difficult to be modeled with complex phenomena such as the highly resolved fluid-platelet dynamic interactions and the formation of filopodia.…”

Margination Regimes and Drainage Transition in Confined Multicomponent Suspensions

“…Engineering the margination process has been proposed for microfluidic cell separations in blood (e.g. [5]) as well as for enhanced drug delivery to the vasculature [6].Direct simulations of flowing multicomponent suspensions -models of blood -can capture margination phenomena [7][8][9][10][11][12][13][14][15][16], but developing a fundamental understanding of underlying mechanisms and parameterdependence from simulations is difficult. It is thus important to have a simple yet mechanistic mathematical model, ideally one with closed form solutions that reveal parameter-dependence, that can distill out the essential phenomena that drive segregation and capture the key effects and transitions.…”

Multi-scale biological and physical modelling of the tumour micro-environment

“…Here, the Stokes/Navier-Stokes equations are not solved, rather, plasma and cell interiors (assumed fluid) are represented by a number of interacting particles (notionally representative of groups of molecules) whose ensemble behaviour statistically returns the appropriate dynamics of the system. Among other particle based methods (molecular dynamics, smoothed particle hydrodynamics), dissipative particle hydrodynamics (DPD) has been widely used recently in the flowing blood simulation literature [1][2][3]30,31]. The principal advantage of these methods is that deforming cell membranes can be treated straightforwardly (possibly also using a DPD model) [4,32,33], as can certain molecular-scale physics (e.g.…”

“…Recent examples include sickle cell anemia [1][2][3], malaria [2,4], haemolysis [5], hemostasis/thrombosis [6,7], aneurism/stenosis [8,9], and cancer metastasis [10][11][12]. Such models can advance our understanding of disease and potentially lead to improved drug and other (e.g.…”