PHASE BEHAVIOR OF REVERSIBLY POLYMERIZING SYSTEMS

可逆聚合体系的相行为

• 批准号: 3351594
• 负责人: JUDITH HERZFELD
• 金额: $ 10.52万
• 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 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3351594
• 关键词: chemical aggregate; chemical binding; computer data analysis; computer simulation; hemoglobin As; hemoglobin Ss; mathematical model; micelles; muscle proteins; phase change; polymerization; protein structure; solute; solutions; solvents; statistics /biometry; surfactant; thermodynamics

The long-term goal of this work is to understand the molecular origins of the phase behavior of reversibly polymerizing systems. This phase behavior forms the basis for such normal processes as the assembly of cytoskeletal elements and cell membranes, and such pathological processes as the polymerization of hemoglobin in sickle cell disease, and the deposition of lipids in atherosclerosis. Studies of these systems have tended to ignore interactions between aggregates. However, these have an important influence on in vivo and in vitro behavior. In the work proposed here we will consider the effects of steric and electrostatic repulsions between aggregates on the size and orientation distributions of the aggregates and on the occurence of phase separation. By taking accunt of the solvent contained in protein polymers, and the possibilities for copolymerization and/or coalignment in mixtures of polymerizing proteins, we will be able to investigate a wider range of the phase behavior of polymerizing proteins than previously possible. By including the possibility of bidirectional growth of micelles, we will be able, for the first time, to explore the biaxial and lamellar phases of surfactants. The theoretical calculations will make use of variations of a lattice model to describe inter-particle interactions and a phenomenological model to describe intra-aggregate interactions. Reference will be made to complimentary experimental work: the theoretical results will inform the design and interpretation of experiments and the experimental data will serve to test theoretical predictions. By elucidating the molecular determinants of the highly cooperative phase behavior of reversibly polymerizing systems, we hope to be able to identify important points of normal and pathological control, and contribute to an improved conceptual framework for therapeutic strategies.

这项工作的长期目标是了解 可逆聚合体系的相行为。 此阶段行为 形成细胞骨架组装等正常过程的基础 元素和细胞膜，以及诸如 镰状细胞病中血红蛋白的聚合和沉积 动脉粥样硬化中的脂质。 对这些系统的研究往往忽视 聚合体之间的相互作用。 然而，这些都有一个重要的 对体内和体外行为的影响。 在这里提出的工作中，我们 将考虑之间的空间排斥和静电排斥的影响 聚集体的尺寸和方向分布 关于相分离的发生。 通过考虑溶剂 包含在蛋白质聚合物中，以及共聚的可能性 和/或聚合蛋白质混合物中的共排列，我们将能够 研究聚合蛋白质的更广泛的相行为 比以前可能的。 通过包括双向的可能性 胶束的生长，我们将能够，第一次，探索 表面活性剂的双轴相和层状相。 理论计算 将利用晶格模型的变化来描述粒子间 相互作用和描述聚合内的现象学模型 互动。 将参考免费的实验工作： 理论结果将为设计和解释提供信息 实验和实验数据将用于检验理论 预测。 通过阐明高度的分子决定因素 可逆聚合体系的协同相行为，我们希望 能够识别正常和病理控制的重要点， 并有助于改善治疗的概念框架 策略。