Nuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components require specialized testing equipment. A computational model permitting cell-specific mechanical information directly from confocal and atomic force microscopy of cell nuclei would be of great value. Here, we developed a computational framework for generating finite element models of isolated cell nuclei from multiple confocal microscopy scans and simple atomic force microscopy (AFM) tests. Confocal imaging stacks of isolated mesenchymal stem cells were converted into finite element models and siRNA-mediated Lamin A/C depletion isolated chromatin and Lamin A/C structures. Using AFM-measured experimental stiffness values, a set of conversion factors were determined for both chromatin and Lamin A/C to map the voxel intensity of the original images to the element stiffness, allowing the prediction of nuclear stiffness in an additional set of other nuclei. The developed computational framework will identify the contribution of a multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on simple nuclear isolation protocols, confocal images and AFM tests.

核力学正在成为干细胞功能和分化的关键组成部分。虽然核结构的变化可以用共聚焦显微镜进行视觉成像，但核及其亚细胞成分的机械特性需要专门的测试设备。允许直接从细胞核的共聚焦和原子力显微镜获得细胞特异性机械信息的计算模型将具有重要价值。在这里，我们开发了一个计算框架，用于从多个共聚焦显微镜扫描和简单的原子力显微镜 (AFM) 测试中生成孤立细胞核的有限元模型。将分离的间充质干细胞的共聚焦成像堆栈转换为有限元模型和 siRNA 介导的 Lamin A/C 消耗分离染色质和 Lamin A/C 结构。使用 AFM 测量的实验刚度值，为染色质和 Lamin A/C 确定了一组转换因子，以将原始图像的体素强度映射到元素刚度，从而可以预测另一组其他核中的核刚度. 开发的计算框架将识别大量亚核结构的贡献，并基于简单的核隔离协议、共焦图像和 AFM 测试预测多个核的全局核刚度。