Structural Adaptation of Microvascular Networks to Mechanical Stimuli

这项研究项目的目标是开发和测试微血管系统的数学模型，该模型包括表征单个血管如何对局部血压和血流做出反应的适应性规则。微血管的半径决定血压和血流量。反过来，通过血管适应的过程，血压和血流决定了微血管半径。这种适应过程本质上是复杂的，因为每个血管都对局部机械刺激做出反应，但网络中的所有微血管似乎都以协调的方式调整其半径，以确保血液供应与组织需求相匹配。这个项目的中心假设是，对于准确预测血管半径的测量变化来说，预先确定平衡条件的“设定点”传统假设是不必要的。这项工作将表征动物模型中完整的微血管网络结构，基于基本原理构建数学模型，并测试系统对血管闭塞的预测响应。这项工作挑战了目前对决定微血管结构的机制的理解。它建立在已建立的数学模型基础上，使用一种独特的动物模型，允许进行非侵入性测量，并由基于研究密集型社区模型的大型多层次研究计划的参与者进行。综上所述，这项工作有望扩大目前对相对简单的适应性规则如何导致微血管系统中的协调反应的理解。研究密集型社区模式由本科生和研究生导师组成的多学科团队组成，他们希望接触到真实的科学研究，而研究生导师则希望接触到真实的研究管理经验。这种新的模式极大地增加了本科生参与原创研究经验的数量，提供了一个有利于招收未被充分代表的学生投身科学和工程职业的环境，通过提供领导不同多学科研究团队的机会来培养研究生成为领导者，并有效地实施了同行教学、跨学科教育、基于团队的问题解决和学习社区的概念。

The objective of this research project is to develop and test a mathematical model of the microvasculature that includes adaptive rules characterizing how individual vessels respond to regional blood pressures and flows. The radii of microvessels determine blood pressure and blood flow. In turn, via the process of vascular adaptation, blood pressure and flow determine microvessel radii. This adaptive process is inherently complex, because each vessel responds to local mechanical stimuli, and yet all the microvessels in a network appear to adapt their radii in a coordinated manner to ensure blood supply matches tissue demand. The central hypothesis of this project is that the conventional assumptions of "set points" that predetermine equilibrium conditions are not necessary to accurately predict measured changes in vessel radii. This work will characterize the structure of intact microvascular networks in an animal model, construct a mathematical model based on fundamental principles, and test the predicted responses of the system to vascular occlusion.This work challenges the current understanding of the mechanisms that determine microvascular architecture. It builds upon established mathematical models, uses a unique animal model that allows noninvasive measurements, and is performed by participants of a large-scale multilevel research program based on a Research-Intensive Community model. Taken together, this work promises to extend the current understanding of how relatively simple adaptive rules lead to a coordinated response in the microvasculature. The Research Intensive Community model partners multidisciplinary teams of undergraduates, who want exposure to authentic scientific research, with graduate student mentors, who want exposure to authentic research management experience. This novel model radically increases the number of undergraduates participating in original research experiences, provides an environment conducive to recruiting underrepresented students to science and engineering careers, prepares graduate students to be leaders by providing opportunities to lead diverse multidisciplinary research teams, and efficiently implements the concepts of peer-teaching, interdisciplinary education, team-based problem solving, and learning communities.