CAREER: Functional Chemical Models of Complex Biochemical Networks

芝加哥大学的Rustem Ismagilov教授在分析和表面化学项目的支持下，利用微流体装置中的化学反应来模拟复杂的生化反应网络。要研究的生化系统是止血——体内溶蛋白、表面结合蛋白和血小板导致血液凝固的一系列大约80种反应。构建起始、抑制和沉淀三个模块，并相互连接。微流控装置内的连续流动将使反应远离平衡状态。定量的实验和理论方法将被用来分析系统的自我修复能力作为一个函数的剪切速率，损坏补丁的大小，流体流动的细节和微流控通道的几何形状。这些方法将有助于产生和检验描述止血功能和循环系统演变的假设。PI通过与芝加哥科学技术博物馆合作，参与制作演示套件，向公众解释化学、复杂性和微流体的价值。功能性生化反应网络是复杂且难以理解的，因为系统的特性来自于单个反应的相互作用。模型必须包括非线性反应动力学、分区化、扩散和流动等效应。微流体技术的最新进展是，化学反应在芯片上狭窄的毛细血管中进行，这使得对这些复杂系统进行详细的研究建模成为可能。

Professor Rustem Ismagilov of the University of Chicago is supported by the Analytical and Surface Chemistry program to model a complex biochemical reaction network using chemical reactions in a microfluidic device. The biochemical system to be studied is hemostasis -the series of eighty or so reactions of soluble proteins, surface-bound proteins and platelets in the body leading to blood clotting. Three modules corresponding to initiation, inhibition and precipitation will be constructed and linked to each other. The reactions will be maintained away from equilibrium using continuous flow inside the microfluidic device. Quantitative experimental and theoretical methods will be used to analyze the ability of the system to repair itself as a function of the shear rate of flow, the size of the damaged patch, the details of fluid flow and geometry of microfluidic channels. The methods will be useful for generating and testing hypotheses describing the function of hemostasis and evolution of circulatory systems. The PI is involved in making demonstration kits that explain the value of chemistry, complexity and microfluidics available to the public through work with the Museum of Science and Technology in Chicago.Functional biochemical reaction networks are complex and difficult to understand because properties of the system arise from the interactions of individual reactions. Models must include effects such as nonlinear reaction dynamics, compartmentalization, diffusion and flow. Recent advances in microfluidics, in which chemical reactions are run in narrow capillaries on a chip, permit the detailed investigative modeling of these complex systems.