PHASE BEHAVIOR OF REVERSIBLY POLYMERIZING SYSTEMS

可逆聚合体系的相行为

• 批准号: 3351597
• 负责人: JUDITH HERZFELD
• 金额: $ 8.83万
• 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 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3351597
• 关键词: chemical aggregate; chemical binding; computer data analysis; computer simulation; mathematical model; model design /development; molecular asymmetry; phase change; polymerization; solutions; statistics /biometry; thermodynamics

Polymerizing proteins are important determinants of the morphological, rheological and osmotic properties of cells, in both pathological states (e.g., sickle cell disease) and normal physiology (e.g., cytoskeletal structure). The distinctive behavior of polymerizing proteins results from the formation of long rigid particles which align spontaneously due to packing constraints. Previous theories have treated the polymerization and alignment as independent processes. However, because the polymerization is reversible, the distributions of polymer lenghts and orientations are reciprocally coupled and evolve jointly. The results of our preliminary calculations show that this view provides a better explanation for calorimetric and osmotic pressure measurements on sickle cell homoglobin than previous descriptions. However, the simple form of the model employed in this initial work could not address other important issues relevant to biochemical systems. We therefore propose to develop more appropriate models which will enable use to examine the effects of polymer structure, nucleation limited polymer numbers, anisotropic interparticle interactions, protein heterogeneity and the binding of small regulatory molecules. The theoretical development will be guided by comparison of the predicted thermodynamics with that observed by osmotic pressure measurements on systematically varied solutions of sickle cell homeglobin and other polymerizing proteins. The results will be used to elucidate the osmotic behavior of erythrocytes in sickle cell disease as reflected in the distribution of cell densities observed under various conditions. By identifying the most critical determinants of the phase behavior of sickle cell hemoglobin, our analysis will provide an improved conceptual framework for the development of therapeutic strategies. These studies will also provide a better understanding of factors influencing the organization of cytoskeletal proteins into fibrillar structures.

聚合蛋白是形态学的重要决定因素， 两种病理状态下细胞的流变学和渗透特性 （例如，镰状细胞病）和正常生理（例如，细胞骨架 结构）。 聚合蛋白质的独特行为源于 形成长刚性颗粒，由于以下原因自发排列 包装限制。 以前的理论已经处理了聚合和 对齐作为独立的过程。 然而，由于聚合反应是 可逆，聚合物长度和方向的分布是 相互耦合、共同发展。 我们初步的结果 计算表明这个观点提供了更好的解释 镰状细胞同红蛋白的量热和渗透压测量 比之前的描述。 然而，所采用的模型的简单形式 在这项初步工作中无法解决与 生化系统。 因此我们建议制定更合适的 可以用来检查聚合物结构影响的模型， 成核限制聚合物数量，各向异性颗粒间相互作用， 蛋白质异质性和小调节分子的结合。 这 理论发展将通过预测的比较来指导 热力学与通过渗透压测量观察到的 系统地改变镰状细胞同源珠蛋白和其他物质的解决方案 聚合蛋白质。 结果将用于阐明渗透压 镰状细胞病中红细胞的行为反映在 不同条件下观察到的细胞密度分布。 经过 确定镰刀相行为的最关键决定因素 细胞血红蛋白，我们的分析将提供改进的概念框架 用于制定治疗策略。 这些研究也将 更好地了解影响组织的因素 细胞骨架蛋白转化为纤维结构。