基于浸入边界法研究超弹性红细胞在剪切流中的运动特性

目的 研究微血管中红细胞在剪切流中的运动特性,为阐明血管疾病的发病机制和开展血液循环实验研究提供理论参考。方法 建立具有膜厚度的超弹性红细胞模型,结合反馈力法和有限元浸入边界法,模拟红细胞在血液剪切流作用下的结构变形和运动方式。其中,固体采用超弹性材料,利用有限单元法进行求解;流体为不可压缩牛顿流体,利用有限差分法求解。结果 数值计算结果重现了细胞在剪切流中以“坦克履带式”向前滚动的运动方式。计算结果与文献结果吻合较好,验证了计算方法的可靠性。结论 所采用的浸入边界法对处理大变形问题的优势尤为明显,可以较好地展示红细胞在剪切流中的变形全过程。     

基于液固耦合的光镊拉伸红细胞变形特性

目的:通过液固耦合的方法模拟红细胞在光镊拉伸过程中的变形情况,从而得到其剪切模量等力学参数,以探索其变形规律。方法:通过PRO/E建立血细胞三维双凹椭球模型,导入到ABAQUS软件中,采用超弹性材料,通过流体腔模型实现液固耦合,对光镊拉伸红细胞模型进行有限元计算。仿真再现红细胞变形的整个过程,拟合Suresh试验数据得到红细胞的剪切模量,进一步分析细胞质、细胞大小和形状与变形能力的关系。结果:仿真得到正常红细胞的剪切模量在5~9μN/m之间;细胞形状和直径均对变形能力有一定影响:直径越大,变形能力越差;双凹椭球细胞相对于球形细胞有更好的变形能力。结论:流体腔模型能够高效实现液固耦合,较好地模拟红细胞在光镊拉伸过程中的变形情况,直观地揭示细胞质、细胞大小和形状与变形的关系。为研究其他壳液提供了一种方法和参考。     

基于超弹性模型的动脉血管数值计算

目的：实验研究表明。血管在周向与轴向两种单轴向拉伸作用下表现出不同的力学特性,本文通过对血管单轴拉伸的数值计算,给出分别适用于周向和轴向荷载的模拟方法。方法：基于超弹性本构模型对轴向和周向两种单轴拉伸作用下血管的应力一应变关系进行数值计算,并结合血管组织结构特点及模型适用范围对结果进行分析,同时通过数值计算对Holzapfel．Gasser-Ogden模型中的各向异性参数对结果的影响展开讨论。结果：计算结果显示单一使用各向同性超弹性应变势函数无法准确完整的模拟两种情况下的单轴拉伸实验,周向拉伸采用各向同性超弹性本构模型的数值结果较好的吻合实验,而轴向拉伸宜采用Holzapfel-Gasser-Ogden模型。Holzapfel。Gasser-Ogden模型中各向异性参数1描述血管中两组增强纤维主方向的分散程度,y值越大即纤维平均主方向与轴向加载方向夹角越小,在外荷载作用下越容易使得纤维旋转到荷载方向;参数K描述血管中每组增强纤维主方向上纤维的分散程度。K值越大,纤维在基体中分散越广泛,材料性子越接近纤维,宏观表现越硬。结论：本文基于超弹性本构模型对轴向和周向两种单轴拉伸作用下血管的应力应变关系进行数值计算,提出分别用多项式形式的各向同性超弹性本构模型数值计算周向荷载作用下应力应变关系、Holzapfel-Gasser-Ogden各向异性超弹性本构模型数值模拟轴向荷载下力学性质,数值结果与实验吻合较好,为心血管系统的数值模拟提供指导,对血管系统的力学机制和临床研究具有重要意义。     

脂肪组织压缩实验中摩擦系数对力学响应的影响

目的针对当前摩擦力对脂肪组织无约束压缩实验结果影响的不确定性,研究压缩实验中合适的摩擦系数设置及适用于模拟脂肪组织生物力学响应的材料本构模型。方法构建低应变率(0.2s^-1)和中应变率(20s^-1)下的脂肪组织有限元模型,分别应用LS-DYNA中常用于模拟脂肪组织的线性黏弹性材料本构、Mooney-Rivlin超弹性材料本构、Ogden超弹性材料本构、软组织材料本构,在不同摩擦系数下进行无约束压缩实验,分析不同摩擦系数及本构模型对接触力大小的影响。结果4种材料本构模型在低、中应变率下,输出的接触力均与摩擦系数呈正相关,有摩擦时的接触力比无摩擦时的接触力大50%左右。中应变率下脂肪组织的力学响应对摩擦系数的灵敏度比低应变率下的更高,且不同材料本构模型输出的接触力差异显著。结论在脂肪组织无约束压缩实验中,静摩擦系数取0.1,动摩擦系数取0.05是合理的,在低、中应变率下Ogden超弹性材料本构能够良好地反映脂肪组织的生物力学响应。     

成骨细胞的体外剪切应力加载实验的变形分析及信号转导区域探讨

目的 根据已有体外培养鼠成骨细胞的参数实验数据,估算剪切应力加载实验中细胞整体剪切形变,借以研究细胞的主要转导区域.方法 计算过程采用黏弹性力学理论,对细胞运用了标准黏弹性模型,并简化其膜所受剪切力为均匀.结果 细胞剪切力产生的细胞变形大约是引起成骨细胞相同生物学响应的拉伸加载变形的十分之一.结论 从细胞总的力学刺激生物学响应来看,剪切应力加载实验中细胞的整体变形所产生的力学转导是可以忽略的,主要转导区域在承受剪切应力的细胞膜.     

离体狐眼外肌被动行为的超弹性分析

目的确定眼外肌的Ogden超弹性模型参数剪切模量(μ)和曲率(α),通过数值模拟为临床眼外肌手术提供理论依据。方法通过单轴拉伸实验测试离体狐眼外肌的被动行为,并用一阶Ogden超弹性模型及ABAQUS软件对其进行超弹性分析。结果实验结果表明,狐眼外肌的被动行为是非线性的。获得了相应的超弹性参数值,其中μ=(16.57±3.76)kPa,α=8.16±1.63。当应变大于6%时,一阶Ogden模型的计算结果与实验结果之间没有显著性差异(P0.05)。计算结果与数值模拟结果都能很好地拟合实验结果。结论所确定的超弹性参数可作为狐眼外肌数值建模的输入量。     

红细胞冻干保存中的渗透性损伤实验研究

红细胞长期保存中保护剂添加、洗涤过程会引入红细胞渗透性损伤.在冻干保存研究中,由于多种保护剂同时使用,保护剂的类型和功能一直是研究的重点,但很少有从渗透性损伤角度分析保存方案合理性的报道.目前相关文献、专利中所用的保护剂总渗透压差别很大,细胞保存后回收率差异也较大.文中用NaCl溶液实验模拟红细胞保存中保护剂添加、洗涤过程.结果表明,选择合适的添加、洗涤方法可以在一定程度上减小渗透损伤.就红细胞而言,1.5Osmol/kg左右是保护剂总渗透压的一个重要阈值,总渗透压低于该阈值时,渗透性损伤较小;高于该阈值时,渗透损伤随着渗透压的增大而迅速增大.所以选择保护剂时,首先应该根据总渗透压来排除渗透压过高的保存方案,否则红细胞在添加和洗涤保护剂时已经损伤很大.该研究对其它细胞长期保存中保护剂的选择也具有参考意义.     

基于超黏弹性的牙周膜本构模型构建及模拟

为了准确描述牙周膜的生物力学行为,基于大变形连续介质力学理论及不可压缩各向同性假设,以人体牙周膜平面剪切和应力松弛实验数据为基础,利用有限元软件ABAQUS的数据拟合功能,构建牙周膜的超黏弹性本构模型及参数。随后,通过对5组牙周膜平面剪切实验过程的模拟,验证牙周膜超黏弹性模型的正确性。最后,通过有限元计算对比分析牙周膜线弹性模型与超黏弹性模型对载荷的力学响应。结果表明在牙根位移量为0～0.06 mm时,牙周膜可近似用线弹性模型表示;当位移量大于0.06 mm,两种模型的差异显著,超黏弹性模型更加符合牙周膜的材料特性。研究结果为牙周膜提供一种实用性强的超黏弹性模型,为牙齿正畸的生物力学研究和治疗方案的精确设计提供理论依据。     

心肌细胞电脉冲作用下电场分布仿真结果与分析

目的 细胞电脉冲刺激仿真是研究心脏电脉冲消融的一种仿真方式，本文建立椭球形细胞电脉冲刺激仿真模型，模拟心肌细胞受到电脉冲刺激下的情况，研究电场入射方向和细胞长度对其电场分布和跨膜电位的影响。方法 通过COMSOL5.5软件进行仿真，以球形细胞模型为基础，在边长60μm的立方体空间中建立椭球形细胞模型。于垂直于Z轴的两面施加2.4 V电压，用以模拟心肌细胞在外加匀强电场作用下的电压分布情况。改变脉冲电场与细胞长轴的夹角，研究0°、30°、60°、90°的不同电场入射角度对心肌细胞电压分布和跨膜电位的影响。保持入射角为0，研究跨膜电位最大值与细胞长轴直径的关系。结果 对于椭球形的心肌细胞，电场的入射角从0°增大到90°时，跨膜电位从1.068 V减小至0.373 V，同时最大跨膜电位的位置也发生改变。入射角为0°时，跨膜电位最大值V与细胞长轴直径D的线性回归方程为V=81.191 6+38.607 9D,r²=0.998 1。结论 电场入射角越大，细胞跨膜电位越低；细胞长轴直径越长，跨膜电位最大值越大。该研究对后续心肌细胞电脉冲刺激实验及心脏电脉冲消融的临床试验具有参...     

声衰减与非线性对双频聚焦声焦域的影响

目的：探讨声衰减与非线性对双频聚焦超声声焦域的影响。方法：利用瑞利积分的线性叠加算法数值模拟计算。并在辐照离体生物组织中进行实验验证。结果：随着声衰减系数的增大与非线性的增强．双频声焦域从“椭球形”变成“蝌蚪形”,并且焦域向着换能器方向移动,但声衰减的影响较非线性大。结论：声衰减与非线性对焦域影响较大,在实际应用中应予考虑。本文在利用瑞利积分的线性叠加算法,研究了媒介声衰减与高声强引起的非线性对差频相干模式下的双频聚焦声场焦域的影响。结果表明,随着声衰减系数的增大与非线性的增加。双频声焦域从“椭球形”变为“蝌蚪形”．并且焦域向着换能器方向移动．但声衰减的影响较非线性大。并在离体牛肝的损伤实验中得到初步验证。     

Resting shape and spontaneous membrane curvature of red blood cells.

A boundary-value problem is formulated describing the biconcave resting shape of normal red blood cells, based on local constitutive equations for the membrane tensions and bending moments. The fundamental physical assumption is that curvature-dependent anisotropic membrane stress resultants accompanied by isotropic bending moments arise from isotropic tensions developing in each leaflet of the lipid bilayer, while the cytoskeleton is unstressed in the resting configuration. Families of equilibrium resting shapes parametrized by the spontaneous bilayer curvature and cell sphericity compare favourably with the average shape of normal red blood cells. The successful comparison supports Helfrich's notion of a non-zero spontaneous curvature whose magnitude is nearly equal to the negative of the equivalent cell radius defined with respect to the membrane surface area. The structure of the solution space suggests a minimum spontaneous curvature below which the cell sphericity is lower than that of the red blood cell, independent of the transmural pressure. The computed cell shapes also compare favourably with the shapes of swollen red blood cells, though for a different value of the spontaneous curvature. The dependence of the spontaneous curvature on the cell volume is attributed to in-plane elastic tensions developing due to the deformation of the cytoskeleton. An alternative formulation based on a non-local model for the monolayer tensions is found to be incapable of predicting non-spherical shapes.     

Numerical Simulation of the Flow-Induced Deformation of Red Blood Cells

A theoretical model is presented for describing the flow-induced deformation of red blood cells. The cells are modeled as deformable liquid capsules enclosed by a membrane that is nearly incompressible and exhibits elastic response to shearing and bending deformation. In the mathematical formulation, the hydrodynamics is coupled with the membrane mechanics by means of surface equilibrium equations expressed in global Cartesian coordinates. Numerical simulations are carried out to investigate the deformation of a cell in simple shear flow, in the physiological range of physical properties and flow conditions. The results show that the cell performs flipping motion accompanied by periodic deformation in which the cross section of the membrane in the plane that is perpendicular to the vorticity of the shear flow alternates between the nearly biconcave resting shape and a reverse S shape. The period of the overall rotation is in good agreement with the experimental observations of Goldsmith and Marlow for red blood cells suspended in plasma. Parametric investigations reveal that, in the range of shear rates considered, membrane compressibility has a secondary influence on the cell deformation and on the effective viscosity of a dilute suspension. The numerical results illustrate in quantitative terms the distribution of the membrane tensions developing due to the flow-induced deformation, and show that the membrane is subjected to stretching and compression in the course of the rotation. © 2003 Biomedical Engineering Society. PAC2003: 8719Tt, 8380Lz, 8717Aa     

Red blood cell proteomics

Since its discovery in the 17th century, the red blood cell, recognized in time as the critical cell component for survival, has been the focus of much attention. Its unique role in gas exchange (oxygen/CO₂ transport) and its distinct characteristics (absence of nucleus; biconcave cell shape) together with an – in essence – unlimited supply lead to extensive targeted biochemical, molecular and structural studies. A quick PubMed query with the word “erythrocyte” results in 198 013 scientific articles of which 162 are red blood cell proteomics studies, indicating that this new technique has been only recently applied to the red blood cell and related fields. Standard and comparative proteomics have been widely used to study different blood components. A growing body of proteomics literature has since developed, which deals with the characterization of red blood cells in health and disease. The possibility offered by proteomics to obtain a global snapshot of the whole red blood cell protein make-up, has provided unique insights to many fields including transfusion medicine, anaemia studies, intra-red blood cell parasite biology and translational research. While the contribution of proteomics is beyond doubt, a full red blood cell understanding will ultimately require, in addition to proteomics, lipidomics, glycomics, interactomics and study of post-translational modifications. In this review we will briefly discuss the methodology and limitations of proteomics, the contribution it made to the understanding of the erythrocyte and the advances in red blood cell-related fields brought about by comparative proteomics.     

温度对单个人红细胞膜力学特性的即时作用

目的：探讨温度对单个红细胞膜力学性质的即时影响。 方法： 利用静态显微图像分析技术和动态显微图像分析技术，在无损、实时、在位的情况下，观察和测量不同温度下单个人红细胞的形态、大小、膜弯曲弹性模量和剪切弹性模量的变化。 结果： 红细胞的接触面积和直径随温度的升高而减小，胞膜的弯曲弹性模量和剪切弹性模量都在生理温度37 ℃时最小，而温度低于或高于37 ℃时红细胞膜的弯曲弹性模量和剪切弹性模量都增大。 结论： 红细胞在生理温度37 ℃时有最好的形态和力学变形性，便于发挥其生理功能。     

The human erythrocyte has developed the biconcave disc shape to optimise the flow properties of the blood in the large vessels

The human erythrocyte adopts a distinctive biconcave disc form in vivo. The question as to why the red blood cell should have this particular profile remains unresolved. It has been suggested that this shape maximises the surface area to volume ratio and thus expedites diffusion. This hypothesis, however does not stand up to examination. Maximal diffusion occurs in the small vessels. In order to pass through the microvasculature the erythrocyte becomes distorted and deviates from the biconcave disc shape [Branemark PI, Lindstrom J. The shape of circulating blood corpuscles. Biorheology 1963;1:139; Guest MM, Bond TP, Cooper RG, Derrick JR. Red blood cells: change in capillaries. Science 1963;142:1319-21]. Here, it is suggested the haemodynamic factors have dictated the peculiar shape of the discocyte. The deleterious nature of turbulent flow on the cardiovascular system suggests that the biconcave disc form has evolved out of a necessity to maximise laminar flow, minimise platelet scatter which in turn suppress atherogenic activity in the large vessels [Yoshizumi M, Abe J, Tsuchiya K, Berk BC, Tamaki T. Stress and vascular responses: athero-protective effect of laminar fluid shear stress in endothelial cells: possible and mitogen-activated protein kinases. J Pharmacol Sci 2003;9:172-6]. The biconcave profile of the discocyte means that much of the mass is distributed in the periphery. This increases the moment of inertia of the cell and subsequently renders the erythrocyte less prone to rotation during flow in the large vessels. Here it is suggest that this reduction in rotation promotes laminar flow and discourages platelet scattering by minimising the "Eddy currents" and it thus anti-atherogenic. A number of pathological mutations result in the red blood cell adopting a spherical shape as opposed to the biconcave disc profile. The sphere has a smaller moment of inertia when compared to the discocyte, as much of the mass is distributed round the centre. The spherocyte is hence much more prone to rotation during flow in the large vessels. There is evidence to suggest that asplenic individuals suffering from spherocytosis are at increased risk of atherogenic cerebrovascular and cardiovascular large-vessel disease, when compared with their asplenic haematological normal counterparts [Schilling RF. Spherocytosis, splenectomy, strokes and heart attacks. Lancet 1997;350:1677-8; Robinnette CD, Fraumeni Jr JF. Splenectomy and subsequent mortality in veterans of the 1939-1945 war. Lancet 1977;ii:127-9].     

Human erythrocytes possess a cytoplasmic endoskeleton containing beta-actin and neurofilament protein

The biconcave disc shape of mammalian erythrocytes has been considered to be maintained only with a membrane underlain by a membranous cytoskeleton. Our improved ion-etching/scanning electron microscopy and saponin-ethanol treatment combined with immunocytochemistry in the human red blood cell revealed the three-dimensional structure of this cytoplasmic endoskeleton apart from the classical membranous cytoskeleton. The endoskeletal meshwork images obtained by the saponin-ethanol treatment corresponded to those by the repeated ion-etching method. The actin-rich endoskeleton was divided into two layers, one superficial and the other deep. The superficial filaments were perpendicularly connected to the membranous cytoskeleton, while the deep filaments formed an irregularly directed complicated meshwork. In the transitional hillside region between the convex periphery and concave center, the endoskeletal filaments containing a neurofilament protein ran parallel to the hillside slope toward the concave center. The endoskeleton of the erythrocyte associating with the membranous cytoskeleton may serve to keep its unique biconcave disc shape deformable, pliable, and restorable against external circumstances.     

Effects of shape and size on red blood cell deformability: a static bending analysis

When flowing down a tapered tube, such as a narrow capillary, red blood cells (RBCs) are subject to deformation, the first event of which is folding in a pancake manner. The RBC deformability is reduced during cell ageing, a phenomenon that may reflect alterations in intracellular viscosity, membrane rigidity or RBC shape. Age related shape changes and their importance for increased RBC rigidity were theoretically analysed. The average empirically observed RBC profile is shown to offer little resistance to bending as compared to other, theoretically possible profiles of the same membrane area and RBC volume. Because of a decrease in projected area (diameter size), and therefore in pressure load, the pressure needed to initiate folding of an old RBC is between 20 and 55% higher than that required to fold a young one if, during RBC ageing, membrane area to cell volume ratio is constant as empirically observed. This difference exists whether the RBC is mathematically treated as a solid body or as a membrane shell.     

Cell ageing for 1 day alters both membrane elasticity and viscosity

This study was designed to focus on the influences of ageing on membrane elasticity and membrane viscosity. The method used was that of postfusion red blood cell oscillation, since this does not require contact between the cells and a mechanical device to apply reproducible forces to the membrane. Freshly drawn human red blood cells were compared with cells from the same donors drawn 24 h earlier and stored at 20 degrees C. The measurements of the oscillation's first pump event time constant and the first swell phase duration revealed no significant changes between fresh and aged cells. Geometrical cell parameters alone were insufficient to characterise changes in the mechanical membrane properties, since some did not vary significantly whereas others did. On the other hand, measurement of the rates of change of geometrical parameters showed that both the membrane elasticity and viscosity modules were increased after the ageing period. Elasticity and viscosity influences could be separated because the durations of the two phases of the cell oscillations differ by three orders of magnitude. Further evidence is provided that the measurement of mechanical membrane characteristics of aged red blood cell must incorporate measurements of membrane surface properties rather than cell volume properties.     

红细胞膜通道力学效应的探讨

在考察红细胞双凹碟形体形成的基础上,讨论了红细胞的输氧功能与红细胞变形的关系,揭示了红细胞膜通道的力学效应:当红细胞呈双凹碟形时,PiPo的地方,红细胞膜通道有释放出氧的现象,其氧的总流率为 J=Lo_2(Pio_2-Poo_2) Lp(Pi-Po) 式中Lo_2为O_2分压差引起的膜通道对氧的流导,PiO_2、Poo_2为膜内外的氧分压;Lp为由于压差引起的膜通道对氧的流导。