Multi-scale modelling of blood flow in sickle cell disease

在镰状细胞病（SCD）中，红细胞（rbc）在缺氧条件下变硬，增加有效血液粘度，如果不及时治疗，最终导致血管完全闭塞。为了指导遗传和药物治疗策略的发展，我们需要了解导致血管闭塞的生物物理过程，以及治疗后血液特性如何影响闭塞风险。为此，在这个项目中，我们将定量地描述导致微通道中可变形和刚性颗粒悬浮液堵塞动力学的因素。使用称为BioFM的流固相互作用代码框架，我们将RBC刚度的分布与有效的血液材料特性和堵塞动力学联系起来。该结果将为非布朗悬浮液中非均匀颗粒特性和非牛顿连续体动力学之间的联系提供新的数学见解，并应用于整个软物质和生物物质。该项目将包括与教授的合作。David Wood（明尼苏达大学）和John Higgins（哈佛医学院），允许学生访问新出现的实验数据。此外，学生将学习高度可转移的编码、模拟和分析技能。该项目符合首席申请人关于复杂生物系统多尺度建模的更广泛的研究计划。研究Areas1。数学生物学2。流体力学与空气动力学连续介质力学

In sickle cell disease (SCD), red blood cells (RBCs) stiffen in deoxygenated conditions, increasing effective blood viscosity and eventually causing complete occlusion of blood vessels, if left untreated. To guide the development of genetic and pharmacological treatment strategies, we need to understand the biophysical processes that lead to vessel occlusion, and how blood properties after treatment affect occlusive risk. To this end, in this project we will quantitatively characterise the factors that contribute to the clogging dynamics of suspensions of deformable and rigid particles in microchannels. Using a fluid-structure interaction code framework called BioFM, we will connect distributions of RBC stiffnesses to effective blood material properties and clogging dynamics. The results will provide new mathematical insight into the connection between heterogeneous particulate properties and emergent non-Newtonian continuum dynamics in non-Brownian suspensions, with applications throughout soft and biological matter. The project will include collaboration with Profs. David Wood (University of Minnesota) and John Higgins (Harvard Medical School), allowing the student to access newly emerging experimental data. Furthermore, the student will learn highly transferable coding, simulation and analytical skills. The project fits into the lead applicant's wider research programme on multi-scale modelling of complex biological systems.Research Areas1. Mathematical Biology 2. Fluid dynamics and aerodynamics 3. Continuum mechanics