微循环中毛细血管表皮蛋白层对剪切流场的响应机理及与血液微流变的耦合研究

Microcirculation vascular system is the final part in human body realizing exchange of oxygen and nutrition materials between blood and tissue. It has the average diameter of several micrometers, comparable with the size of the blood cells. It is also covered by a endothelial glycocalyx layer (EGL), which is nanometers thick and of brushed-like polymer structure. Thus the deformation of EGL under shear flow, its biophysical functions as well as the complex-liquid nature of the confined blood consist of a multiple-mechanism and multiple-scaled microfluidic system. The shear-dependent response of the EGL-blood system plays a significant role in the diseases like hypertension, diabetes and thrombus. In this project we propose a microvascular boundary lubrication model and theory to combine the viscoelastic deformation of the EGL, the permeability of the porous boundary layer and the microrheology of blood in the vicinity of the EGL. Then the model will be used to reveal the shear-dependentstructural reconstruction and viscoelastic deformation of the EGL, as well as the wall shear stress transmission onto the vessel surface. The microrheology of blood near the EGL surface will also be investigated. The lubrication mechanism within the capillary vesselsand the detailed flow behavior of blood will be experimentally studied by using total internal reflection fluorescence microscopy, confocal microscopy as well as nanoparticle velocimetry. The effects of confinement size, boundary properties of the EGL, hematocrit,temperature and environmental pH values will be investigated and revealed. The corresponding variation of the microrheological properties will be studied, which are believed to be a potential measurable indicator in clinical diagnose. This project will couple the shear-dependent response of EGL and the microrheology of blood, to provide a theoretical base and model for microcirculation mechanics and potential clinical applications.

微循环血管系统是人体获得氧份与营养的终端，其微米级直径与血液红细胞体积相当,内覆的纳米级表皮蛋白层在剪切场下的界面结构变化与血液流动构成了多物理机制与多作用尺度共存的复杂微流体系统，对人体重大疾病如高血压/糖尿病/血栓等的发生机制至关重要。本项目拟建立计入微血管表皮蛋白层粘弹性响应及界面效应与血液微流变的边界润滑流动模型，研究其在各种剪切场下(包括单细胞通过/血管壁挤压流动)的变形规律、结构改变与剪应力传递机制；结合血液的微流变与结构变化，进行微血管流动的在体与离体试验观测，采用全内反射显微镜、共聚焦显微镜及荧光粒子测速技术观测揭示毛细血管中的润滑机理（包括细胞稀释层的规律）,研究不同受限尺度、壁面性质、血液血容比、温度与pH值下的微血管流动行为及其导致的微流变规律。本研究将耦合微血管表皮蛋白质的剪切响应机理与可观测的血液微流变特征,为揭示微循环机理和临床应用提供理论基础和模型依据。

本项目建立了计入微血管表皮蛋白层微结构的界面效应与尺度效益的微血管边界润滑与流动模型，采用渗透系数表征表皮蛋白层的结构特征，并采用Brickman方程，研究分析其在各种剪切场下的变形规律、结构改变与壁面剪应力传递机制；采用典型表皮蛋白层分子及溶液，分析了其成分组成与流变性质，采用石英晶振微天平测试分析了蛋白分子在壁面的吸附过程与规律，揭示了不同受限尺度、壁面性质、温度下微血管壁面的吸附规律，同时测试了微纳米柱状结构的空隙壁面上的阻力分布，与理论计算结果吻合良好；采用微流体荧光观测技术，观测了不同修饰基地表面上结合的蛋白抗体分子的基底结合能力和不同流速剪切响应，揭示了与流体中抗原蛋白分子反应的效率和微循环中壁面剪切应力的传递规律，并将壁面剪切响应规律用于临床血液检测的微芯片的控制技术中。.本项目发表标注论文7篇，已发表SCI收录6篇（均标注），其中基于石英晶振微天平的边界层流体流变响应的综述文章发表在Applied Physics Reviews上，影响因子13.7，获得广泛关注.