DYNAMIC PATTERN IN CHEMICALLY REACTING SYSTEMS

化学反应系统中的动态模式

• 批准号: 2518907
• 负责人: HANS G OTHMER
• 金额: $ 20.35万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518907
• 关键词: Dictyostelium; Escherichia coli; calcium channel; calcium flux; cell cell interaction; cell differentiation; chemotaxis; cyclic AMP; diffusion; egg /ovum; endoplasmic reticulum; heart cell; mathematical model; membrane potentials; microorganism culture; model design /development; sarcolemma; sarcoplasmic reticulum; tissue /cell culture

The long range objectives of this research are to further the understanding of the dynamical behavior of aggregates of interacting cells, and to apply this knowledge to problems of cell movement and pattern formation in developmental biology and to problems in physiology. The research falls into four major categories: (1) studies on pattern formation in development, (2) studies on chemotaxis, (3) studies on excitable systems, and (4) studies on cardiac dynamics. The aim under (1) is to develop and analyze models for mound formation in the cellular slime mold Dictyostelium discideum that incorporate pacemakers, cAMP production and diffusion, cell-cell interactions, cell differentiation and cell sorting. The aim in (2) is to develop and analyze a model for bacterial adaptation and to do simulations of aggregation in three-dimensional concentration fields. The major objective in (3) is to study models of calcium channel dynamics in oocytes with a view toward understanding the effect of different types of calcium channels on the stimulus-response characteristics and the propagation of waves. The aims under (4) are (I) to develop an integrated model for calcium dynamics and the membrane potential in cardiac myocytes in order to understand spontaneous calcium release, and (ii) to study the role of anisotropy in the genesis of fibrillation in ventricular tissue. The results of parts (l) and (2) of this research will advance our understanding of several basic processes in developmental biology: signal transduction, cell-cell signaling, cell and tissue motion and spatial pattern formation. A better understanding of these processes will contribute to a better understanding of how systems respond to their environment, how normal development can be disrupted, and how certain components of the immune system function. The results of the work described under (3) and (4) will further our understanding of one of the major public health problems in the US, sudden cardiac death, which claims approximately 1000 individuals per day. Most result from a rapid irregular rhythm called ventricular fibrillation, which often evolves from ventricular tachycardia. The results of the proposed work will contribute to our understanding of two important aspects of the genesis of arrhythmias. Firstly, single-cell models that incorporate current knowledge about membrane dynamics and calcium handling will advance our understanding of how these components interact and how this interaction can produce ventricular tachycardia locally. Secondly, integrating the single-cell dynamics into a large-scale model of cardiac tissue will provide insight into how aberrant local behavior can be suppressed by interaction with neighboring tissue, what the critical space scale of abnormality is for production of large-scale (tissue-wide) disruption of propagation, and how supercritical local abnormalities evolve in time. A better understanding of the different mechanisms that can give rise to ventricular tachycardia and an understanding of how it evolves into ventricular fibrillation may lead to new strategies for suppressing them and thereby have an important impact on public health.

这项研究的长期目标是进一步 对相互作用集合体动力学行为的理解 细胞，并将这一知识应用于细胞运动和 发育生物学中的模式形成和生理学问题。 本研究主要分为四大类：(1)模式研究 发育中的形成，(2)趋化性的研究，(3)关于 可兴奋系统；(4)心脏动力学研究。第(1)项的目标 是开发和分析细胞黏液中土丘形成的模型 包括起搏器、营地生产的盘基网柄霉菌 和扩散、细胞间的相互作用、细胞分化和细胞 分类。(2)中目标是开发和分析细菌的模型 适配和在三维中进行聚集模拟 浓度场。(3)中的主要目标是研究 卵母细胞内钙通道动力学的研究 不同类型钙通道对刺激反应的影响 波的特性和传播。第(4)款的目的是(I) 开发钙动力学和膜的集成模型 为了了解自发钙离子在心肌细胞中的电位 以及(Ii)研究各向异性在骨质疏松症发生中的作用 脑室组织中的纤颤。 本研究(L)和(2)部分的研究结果将对我们的研究起到推动作用 对发育生物学中几个基本过程的理解：信号 转导、细胞-细胞信号、细胞和组织运动和空间 图案的形成。更好地理解这些过程将会 有助于更好地了解系统如何响应其 环境，如何破坏正常的发展，以及如何确定 免疫系统功能的组成部分。工作的成果 第(3)和(4)项中描述的内容将进一步加深我们对 美国的主要公共卫生问题，心脏性猝死，声称 每天大约1000个人。大多数是由于快速的不规则的 称为室颤的节律，它通常是从 室性心动过速。拟议工作的成果将有助于 对我们理解的两个重要方面的起源 心律不齐。首先，结合了电流的单电池模型 膜动力学和钙处理的知识将促进我们的 了解这些组件如何交互以及这种交互如何 会在局部引起室性心动过速。第二，整合 将单细胞动力学转化为心脏组织的大规模模型 深入了解如何通过以下方式抑制异常的本地行为 与邻近组织的相互作用，什么是临界空间尺度 异常是由于生产的大规模(组织范围)中断 传播，以及超临界局部反常如何随时间演变。一个 更好地理解不同的机制可以引起 室性心动过速及其如何演变为 室颤可能导致抑制它们的新策略 从而对公众健康产生重要影响。