SELF-ASSEMBLY AND SPONTANEOUS ORDER IN CROWDED SOLUTIONS

拥挤解决方案中的自组装和自发秩序

• 批准号: 3351596
• 负责人: JUDITH HERZFELD
• 金额: $ 15.22万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3351596
• 关键词: actin binding protein; actins; biophysics; chemical aggregate; chemical kinetics; computer data analysis; conformation; diffusion; hemoglobin; hemoglobin Ss; intermolecular interaction; micelles; microfilaments; microtubule associated protein; microtubules; molecular shape; monomer; nonblood rheology; phase change; phosphorylation; polymerization; polymers; protein structure; solute; solutions; surfactant; thermodynamics; tubulin

Supramolecular biological structures are formed by the reversible association of amphiphilic molecules into extended aggregates. For example, the reversible self-assembly of cytoskeletal proteins into fiber bundles and networks constitutes the major determinant of the morphological and rheological properties of cells. In caricature, the pathological morphological and rheological properties of the red cells in sickle cell disease derive from the abnormal self-assembly of the mutant hemoglobin into long, thick "polymers'. These self-assembly processes occur in very crowded solutions where interactions between aggregates can lead to spontaneous orientational and positional ordering of the aggregates. Understanding these long-range effects of non-ideality is important for interpreting in vitro and in vivo observations. Statistical mechanical techniques from the field of complex fluids (including ones developed in-house) will be used to elucidate the behavior of both binary (single solute plus solvent) and ternary systems. For binary systems at equilibrium, the goals are to explain the ubiquitous positional ordering seen in micellar surfactant solutions, and to explore the effects of fiber flexibility on orientational ordering in solutions of reversibly "polymerizing" proteins. Studies of the kinetics of binary systems will analyze the effects of crowding on the progress of self-assembly and spatial ordering. For hemoglobin ternary systems, the goals are to understand how non-sickle hemoglobins affect the behavior of sickle cell hemoglobin in heterozygous and double heterozygous individuals. For cytoskeletal ternary systems, studies will explore the effect of interactions between different cytoskeletal fibers and the various ways that the reversible binding of cytoskeletal accessory proteins can influence cytoskeletal structure, both in-homogeneous solutions and with imposed spatial gradients. By elucidating the molecular determinants of the highly cooperative behavior of self-assembling structures under crowded conditions, we hope to be able to identify important points of normal and pathological control, and contribute to an improved framework for therapeutic strategies.

超分子生物结构是由可逆的 两亲性分子缔合成延伸的聚集体。 为 例如，细胞骨架蛋白质可逆地自组装成纤维 束和网络构成了形态的主要决定因素 和细胞的流变学性质。 在漫画中， 镰状细胞红细胞的形态学和流变学特性 由突变血红蛋白的异常自我组装引起的疾病 变成又长又厚的“聚合物” 这些自组装过程发生在非常 拥挤的解决方案，其中聚集体之间的相互作用可能导致 聚集体的自发取向和位置有序化。 了解这些非理想的长期影响对于 解释体外和体内观察结果。 统计力学 复杂流体领域的技术（包括已开发的 内部）将用于阐明二进制（单 溶质加溶剂）和三元体系。 对于二元系统， 平衡，目标是解释无处不在的位置排序 在胶束表面活性剂溶液中看到，并探讨纤维的影响， 可逆问题解中取向序的灵活性 “聚合”蛋白质。 二元体系动力学的研究将 分析拥挤对自组装过程的影响， 空间排序 对于血红蛋白三元体系，目标是 了解非镰状血红蛋白如何影响镰状细胞的行为 杂合子和双杂合子个体的血红蛋白。 为 细胞骨架三元系统，研究将探讨影响 不同细胞骨架纤维之间的相互作用以及 细胞骨架辅助蛋白的可逆结合 影响细胞骨架结构，包括不均匀溶液和 施加空间梯度。 通过阐明 拥挤环境下自组装结构的高度合作行为 在这种情况下，我们希望能够确定正常和 病理控制，并有助于改善框架， 治疗策略