A Computer Model of Engineered Cardiac Monolayers
A Computer Model of Engineered Cardiac Monolayers
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DOI：
10.1016/j.bpj.2010.01.008
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发表时间：
2010-05-05
影响因子：
3.4
通讯作者：
Henriquez, Craig S.
中科院分区：
文献类型：
--
作者：
Kim, Jong M.;Bursac, Nenad;Henriquez, Craig S.
使用微研磨和微图案化方法创建的工程单层提供了一个简化的体外系统来研究各向异性和纤维方向对电传播的影响。解释这些文化系统中的行为通常使用具有连续属性的经典计算机模型来执行。然而，这样的模型不考虑随机的细胞形状，细胞取向，和裂缝空间固有的这些单层上产生的波前传导的影响。这项工作提出了一种新的方法来模拟单层的心脏组织中的因素，细胞的形状，细胞间的耦合，和程度的裂缝空间不是恒定的，而是被视为空间随机分配的分布。这种建模方法使得有可能模拟波前传播的方式类似于工程单层组织上进行实验。模拟结果进行了比较，以前公布的测量数据，从单层用于调查的作用，细胞结构上的传导速度和各向异性比。我们还提出了一个估计，从这些网络中获得的电性能，并演示了离散的细胞结构的变化如何影响宏观电导率。模拟支持的共同假设，在正常范围内的耦合强度，组织与细胞形状和连接性的相对均匀的分布，可以表示使用连续的模型与来自随机离散的细胞结构，使用全球或本地估计的电导率。结果还表明，在细胞取向的突然变化的存在下，组织特性的局部估计预测电导率的平滑变化，这可能不足以预测在过渡部位的传播的离散性质。
Engineered monolayers created using microabrasion and micropatterning methods have provided a simplified in vitro system to study the effects of anisotropy and fiber direction on electrical propagation. Interpreting the behavior in these culture systems has often been performed using classical computer models with continuous properties. However, such models do not account for the effects of random cell shapes, cell orientations, and cleft spaces inherent in these monolayers on the resulting wavefront conduction. This work presents a novel methodology for modeling a monolayer of cardiac tissue in which the factors governing cell shape, cell-to-cell coupling, and degree of cleft space are not constant but rather are treated as spatially random with assigned distributions. This modeling approach makes it possible to simulate wavefront propagation in a manner analogous to performing experiments on engineered monolayer tissues. Simulated results are compared to previously published measured data from monolayers used to investigate the role of cellular architecture on conduction velocities and anisotropy ratios. We also present an estimate for obtaining the electrical properties from these networks and demonstrate how variations in the discrete cellular architecture affect the macroscopic conductivities. The simulations support the common assumption that under normal ranges of coupling strength, tissues with relatively uniform distributions of cell shapes and connectivity can be represented using continuous models with conductivities derived from random discrete cellular architecture using either global or local estimates. The results also reveal that in the presence of abrupt changes in cell orientation, local estimates of tissue properties predict smoother changes in conductivity that may not adequately predict the discrete nature of propagation at the transition sites.