MSM: Adaptive Multi-Scale Model Simulation, Reduction and Integration for Cardiac Muscle Physiology

Bassingthwaighte0506477该项目的目的是为人体生理学的多尺度建模奠定基础，并在心脏和肌肉生理学中具体应用。这些结果将提供跨越多个模型尺度(转录调节、细胞能量代谢、细胞间相互作用、综合器官收缩功能)的计算策略和算法。该项目将开发自适应多尺度建模、模拟和模型简化的方法。该项目将结合(A)肌细胞-平滑肌细胞-内皮细胞相互作用的建模和控制它们的信号，(B)允许这些细胞类型适应变化状态和在伪稳定状态下更有效的计算的自动模型简化，以及(C)在亚细胞水平到整个系统水平的参数识别。模拟结果将通过整合心肌和骨骼肌系统的模型来提供对生理系统行为的新见解，该模型显示了对心脏和骨骼肌中存在的各种生理条件的适应性反应。这项拟议的研究将启动华盛顿大学工程和生命科学专业的教职员工和研究生之间的跨学科合作。

Bassingthwaighte0506477 The aim of the project is to lay the foundations for multi-scale modeling of human physiology with specific application in cardiac and muscle physiology. The results will provide computational strategies and algorithms spanning multiple modeling scales (regulation of transcription, cellular energetic metabolism, cell-to-cell interactions, integrated organ contractile function). The project will develop methods for adaptive multiscale modeling, simulation and model reduction. The project will combine (a) modeling for myocyte- smooth muscle cell-endothelial cell interactions and the signals controlling them, (b) automated model reduction allowing adaptation of these cell types to changing states and more efficient computation in pseudo-steady states, and (c) parameter identification at subcellular to overall systems levels. The simulation results will provide new insights into the behavior of the physiological system by integrating models of cardiac and skeletal muscle systems showing adaptive responses to various physiological conditions that exist in both heart and skeletal muscles. The proposed research will initiate inter-disciplinary collaborations among faculty members and graduate students from engineering and life sciences at the University of Washington.