Engineering design of a cardiac myocyte
Engineering design of a cardiac myocyte
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DOI：
10.1007/s10820-006-9045-6
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发表时间：
2007-04-01
期刊：
影响因子：
--
通讯作者：
Parker, K. K.
中科院分区：
文献类型：
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作者：
Adams, W. J.;Pong, T.;Parker, K. K.
我们描述了一种构建具有特定空间尺寸和生理功能的心肌细胞的设计算法。使用心肌细胞的计算模型，我们以可控的空间维度模拟了心肌细胞中的钙(钙)波动动力学。当原代新生大鼠心肌细胞在微图案化的底物上培养时，所建模型的心肌细胞在体外被复制。肌细胞重塑以符合二维边界条件，并呈现打印的细胞外基质岛的形状。原子力显微镜对心肌细胞的机械扰动导致钙诱导的细胞内钙释放和钙波的传播，如使用细胞内钙荧光指示剂的高速视频显微镜所显示的那样。对测量的波前动力学与计算机模型中模拟的波前动力学的分析和比较表明，工程心肌细胞的行为与模型预测的一致。这些结果很重要，因为它们代表了使用计算机建模、计算机辅助设计和生理实验来设计和验证工程细胞的性能。成功地设计生物细胞和组织用于分析或治疗性植入的能力将需要设计算法和工具来保证质量和监管。
We describe a design algorithm to build a cardiac myocyte with specific spatial dimensions and physiological function. Using a computational model of a cardiac muscle cell, we modeled calcium (Ca2+) wave dynamics in a cardiac myocyte with controlled spatial dimensions. The modeled myocyte was replicated in vitro when primary neonate rat ventricular myocytes were cultured on micropatterned substrates. The myocytes remodel to conform to the two dimensional boundary conditions and assume the shape of the printed extracellular matrix island. Mechanical perturbation of the myocyte with an atomic force microscope results in calcium-induced calcium release from intracellular stores and the propagation of a Ca2+ wave, as indicated by high speed video microscopy using fluorescent indicators of intracellular Ca2+. Analysis and comparison of the measured wavefront dynamics with those simulated in the computer model reveal that the engineered myocyte behaves as predicted by the model. These results are important because they represent the use of computer modeling, computer-aided design, and physiological experiments to design and validate the performance of engineered cells. The ability to successfully engineer biological cells and tissues for assays or therapeutic implants will require design algorithms and tools for quality and regulatory assurance.