MSM: Multi-scale modeling of the mouse heart: from genotype to phenotype

McCulloch 0506252该研究的目的是开发新的小鼠心脏多尺度计算模型，该模型在功能和结构上整合了从分子网络到器官系统的多个生物组织尺度。这些新的正常和基因修饰小鼠心脏的电动力学模型将整合以下生物尺度和数学模型类别：（1）分子调节网络的生物化学模型;（2）整个兴奋-收缩耦合的生物物理模型;（3）多细胞心脏组织的区域各向异性电和机械特性的微结构本构模型;（4）多细胞心脏组织的局部各向异性电和机械特性的微结构本构模型。（4）小鼠心室几何结构、纤维结构和传导系统解剖结构的三维解剖学详细模型;以及（5）循环系统血液动力学的集总参数模型。这项研究将使人们更好地了解正常的心脏以及它在病理生理状态下是如何变得功能障碍的。这项拟议中的研究将启动加州圣地亚哥大学的生物工程师与南卡罗来纳州大学的发育生物学家和解剖学家之间新的跨学科合作。作为这项合作的结果，一个大型的新的多尺度数据资源，将使科学家能够以高分辨率导航整个小鼠心脏解剖结构。

McCulloch0506252The aim of the research is to develop new multi-scale computational models of the mouse heart that integrate functionally and structurally across multiple scales of biological organization from molecular networks to organ system. These new models of the electromechanics of the normal and genetically modified mouse heart will integrate across the following biological scales and classes of mathematical model: (1) biochemical models of molecular regulatory networks; (2) biophysical models of whole excitation-contraction coupling; (3) microstructural constitutive models of the regional anisotropic electrical and mechanical properties of multicellular cardiac tissue; (4) three-dimensional anatomically detailed models of mouse ventricular geometry, fiber architecture and conducting system anatomy; and (5) lumped parameter models of circulatory system hemodynamics. This research will provide better understanding of the normal heart and how it becomes dysfunctional in pathophysiological states.The proposed research will initate a new inter-disciplinary collaboration between bioengineers at University of California San Diego and developmental biologists and anatomists at University of South Carolina. As a result of this collaboration, a large new multi-scale data resource that will allow scientists to navigate whole mouse heart anatomy at high resolution.