Multiscale in silico modeling of the cell-tissue-organ units is an emerging area of research with the potential to improve our understanding of various disease pathogenesis. Using a multiscale modeling approach, we developed a computational model of the human cornea to investigate how the application of macroscale loads may alter the micro-mechanical environment of the cells. We then utilized the multiscale model to study the effect of physiological and non-physiological mechanical loading conditions such as intraocular pressure (IOP) loading, IOP spike, and eye-poking on the corneal cells. On comparing the results obtained under increased IOP and eye-poking loading, we observed large differences in the averaged principal stress magnitudes in the immediate vicinity of the cell through the thickness of the cornea. On the other hand, our model predicted that under physiological IOP loading, the average principal strain magnitudes in the immediate vicinity of the cell remained almost constant irrespective of the cell location in the stroma. To our knowledge, this is the first study that investigates the effect of mechanical loading on the corneal cells through a multiscale modeling framework. Our computational multiscale cornea model provides a platform to perform virtual experiments and test hypotheses to further our understanding of the potential mechanical cause of multiple diseases in the cornea.

多尺度计算机细胞组织器官单位的建模是一个新兴的研究领域，具有提高我们对各种疾病发病机理的理解的潜力。使用多尺度建模方法，我们开发了人类角膜的计算模型，以研究宏观尺度载荷的应用如何改变细胞的微机械环境。然后，我们利用多尺度模型研究了生理和非生理机械负荷条件（如眼内压（IOP）负荷，IOP尖峰和眼睛戳伤）对角膜细胞的影响。通过比较在增加眼压和戳眼负荷下获得的结果，我们观察到在整个眼角膜厚度范围内，细胞紧邻区域的平均主应力大小存在较大差异。另一方面，我们的模型预测，在生理性IOP负荷下，无论基质在细胞中的位置如何，细胞紧邻区域的平均主要应变幅度几乎保持恒定。据我们所知，这是第一项通过多尺度建模框架研究机械负荷对角膜细胞影响的研究。我们的计算性多尺度角膜模型提供了一个平台，可以执行虚拟实验和检验假设，以进一步了解角膜多种疾病的潜在机械原因。这是第一项通过多尺度建模框架研究机械负荷对角膜细胞影响的研究。我们的计算性多尺度角膜模型提供了一个平台，可以执行虚拟实验和检验假设，以进一步了解角膜多种疾病的潜在机械原因。这是第一项通过多尺度建模框架研究机械负荷对角膜细胞影响的研究。我们的计算性多尺度角膜模型提供了一个平台，可以执行虚拟实验和检验假设，以进一步了解角膜多种疾病的潜在机械原因。