3D Dynamics of Protein Network Coupled to Lipid Bilayer in Diseased Erythocytes

患病红细胞中与脂质双层耦合的蛋白质网络的 3D 动力学

• 批准号: 7837360
• 负责人: Qiang Zhu
• 金额: $ 21.11万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7837360
• 关键词: Accounting; Actins; Address; Adopted; Affect; Algorithms; Ankyrins; Architecture; Arts; Behavior; Bio-Base; Biological; Biomechanics; Biomimetics; Blood Circulation; Blood capillaries; Carbon Dioxide; Cell membrane; Cell model; Cells; Cereals; Chemistry; Complex; Coupled; Coupling; Data; Defect; Development; Devices; Diffusion; Disease; Elements; Elliptocytosis found; Engineering; Erythrocyte Anion Exchange Protein 1; Erythrocyte Membrane; Erythrocytes; Foundations; Functional disorder; Glycophorin; Goals; Hand; Head; Hematological Disease; Hereditary Elliptocytosis; Hereditary Spherocytosis; Human; Human body; Hybrids; In complete remission; Indium; Inherited; Interdisciplinary Study; Investigation; Ions; Joints; Knock-out; Knockout Mice; Knowledge; Life; Light; Link; Lipid Bilayers; Lipids; Liquid substance; Literature; Longevity; Measurement; Mechanics; Membrane; Membrane Proteins; Methods; Modeling; Molecular; Molecular Conformation; Molecular Structure; Mutant Strains Mice; Mutation; Non-linear Models; Oceans; Performance; Peripheral; Physiological; Play; Property; Protein Dynamics; Proteins; Publishing; Quantum Dots; Reporting; Research; Rheology; Role; Science; Scientist; Shapes; Signal Transduction; Simulate; Skeleton; Spectrin; Structure; Suspension substance; Suspensions; Techniques; Testing; Time; Transmission Electron Microscopy; Transport Process; Work; base; capillary; design; dimer; flexibility; improved; interest; mechanical behavior; membrane skeleton; multi-scale modeling; mutant; nanoscale; novel; oxygen transport; particle; protein 4.1; research study; response; sensor; simulation; skeletal; southeast Asian; three dimensional structure; three-dimensional modeling; viscoelasticity

6. Project Summary The long term goal of this study is to understand how biological membranes control their structural integrity, dynamical response, and physiological performance. Here we specifically study the erythrocyte membrane which has a protein network coupled to a lipid bilayer. We recently developed a new molecular-based hybrid model for the 3D dynamic response of this coupled structure. The model incorporates a 3D configuration of the junctional complex we predicted, the network topology revealed by transmission electron microscopy, and several interactions between the protein network and the lipid bilayer reported in literatures. By extending this 3D dynamic model, specific aims are proposed to test and model diseased erythrocyte membrane mechanics. The multiple- scale modeling will include the molecular-based hybrid model and a complete cell model with a Finite-Element Method. Models will be tested against published data on mutant human erythrocytes (e.g. hemolytic spherocytosis and elliptocytosis) and new data to be obtained for knockout mouse cells. Experiments will include micropipette aspiration, quasi-static and rate dependent testing and viscoelastic constitutive response with novel microrheology methods. The viscoelasticity will be compared with the molecular-based hybrid model, while the deformation of the cell will be compared with the complete cell model. This work will shed new light into physiological mechanisms by which diffusion/transport, structural sustainability, and signal transduction may be further regulated by the dynamics of the elements in the network at the nano-scale. This knowledge may provide the missing link between molecular organization and biomechanics of the membrane, and improve the understanding and treatment of hematological disorders. The broader impact is a framework to understand a wide class of interesting and important biological membrane structures and paths for biomimetics in synthetic bio-membranes, membrane-based bio-sensors, and other structures. 7. Project Narrative The proposed research will allow us to understand how the three-dimensional molecular organization of the red blood cell membrane provides structural sustainability of the cells and facilitates the diffusion/transport of oxygen and carbon dioxide during circulation. This study will also help us understand how genetic defects in the membrane structure may result in shorter life of red blood cells in hematological disorders. It will also lay a foundation for scientists and engineers to build biologically-inspired structures.

6.项目摘要 这项研究的长期目标是了解生物膜如何控制 它们的结构完整性、动态响应和生理性能。这里我们 特别是研究红细胞膜，它有一个蛋白质网络耦合到一个 脂质双层我们最近开发了一种新的基于分子的3D混合模型， 这种耦合结构的动态响应。该模型采用了3D配置 在我们预测的连接复合体中，通过传输揭示的网络拓扑结构 电子显微镜，以及蛋白质网络和脂质之间的几种相互作用 双分子层的报道。通过扩展该3D动态模型， 提出测试和模型患病红细胞膜力学。多重- 比例模型将包括基于分子的混合模型和一个完整的细胞 用有限元法建立模型。模型将根据已公布的数据进行测试， 突变型人红细胞（例如溶血性球形红细胞增多症和椭圆形红细胞增多症）和新的 需要从敲除小鼠细胞中获得数据。实验将包括微量移液管 抽吸、准静态和速率相关测试以及粘弹性本构 响应与新的微观流变学方法。粘弹性将与 基于分子的混合模型，而细胞的变形将进行比较 完整的细胞模型。这项工作将为生理学研究提供新的思路。 扩散/运输、结构可持续性和信号 转导可以进一步由网络中元件的动力学调节 在纳米尺度上。这些知识可能会提供分子之间缺失的环节， 组织和生物力学的膜，并提高理解和 血液病的治疗。更广泛的影响是一个框架， 广泛的一类有趣的和重要的生物膜结构和路径， 合成生物膜、膜基生物传感器等中的仿生学 结构. 7.项目叙述 这项拟议中的研究将使我们能够了解三维分子是如何 红细胞膜的组织提供了细胞的结构可持续性， 在循环过程中促进氧气和二氧化碳的扩散/运输。本研究将 这也有助于我们了解膜结构中的遗传缺陷如何导致更短的 血液病中红细胞的寿命。它也将为科学家和 让工程师们来建造受生物启发的建筑。