Giannopoulos Dimosthenis, Schlittler Maja, De Bortoli Marzia, Coppini Raffaele, Petrovic Mina, Cerbai Elisabetta, Schütz Gerhard J, Thurner Philipp J, Rossini Alessandra, Andriotis Orestis G
Institute of Lightweight Design and Structural Biomechanics, TU Wien, Vienna, Austria.
Institute for Biomedicine, Eurac Research, Bolzano, Italy.
Sci Rep. 2025 Jun 5;15(1):19825. doi: 10.1038/s41598-025-03676-3.
Mechanically characterizing biological tissues at the microscale helps to better link microscale biomechanics to mechanobiology but also contributes to the mechanistic understanding of disease mechanobiology. Cell spheroids (CSs) are state-of-the-art in vitro three-dimensional cell cultures allowing for the synthesis of microtissue models into sphere-like geometry. Such a geometry is attractive for micromechanical assessment via parallel-plate compression, since only minimal and nondestructive sample preparation is required to conduct such tests. However, appropriate data analysis and interpretation methods are mostly lacking. Current approaches, relying on Hertzian theory and its modifications, are inadequate for capturing large deformations observed in CSs upon compression. Here, we utilized the extended Tatara model, incorporating hyperelasticity and nonlinear boundary effects, to investigate CS mechanics. To evaluate the effectiveness of the model, we compared results to Hertz, Ding, and simple Tatara models. The extended Tatara model demonstrated superior accuracy, enabling mechanical analysis of CSs under compression of up to 50% strain. Estimating the apparent Poisson's ratio via image segmentation and shape analysis helped refine the calculated apparent modulus. This work establishes a robust analytical framework that will, in the future, help advance our understanding of cardiac fibrosis progression and support the development of therapeutic strategies using patient-derived CSs as test models.
在微观尺度上对生物组织进行力学表征,有助于更好地将微观生物力学与力学生物学联系起来,同时也有助于对疾病力学生物学进行机理理解。细胞球状体(CSs)是最先进的体外三维细胞培养物,可将微组织模型合成为球状几何结构。这种几何结构对于通过平行板压缩进行微机械评估很有吸引力,因为进行此类测试只需要最少且无损的样品制备。然而,目前大多缺乏适当的数据分析和解释方法。当前依赖赫兹理论及其修正的方法,不足以捕捉CSs在压缩时观察到的大变形。在此,我们利用扩展的塔塔拉模型,该模型纳入了超弹性和非线性边界效应,来研究CSs的力学特性。为了评估该模型的有效性,我们将结果与赫兹模型、丁模型和简单塔塔拉模型进行了比较。扩展的塔塔拉模型显示出更高的准确性,能够对高达50%应变压缩下的CSs进行力学分析。通过图像分割和形状分析估计表观泊松比,有助于细化计算出的表观模量。这项工作建立了一个强大的分析框架,未来将有助于推进我们对心脏纤维化进展的理解,并支持以患者来源的CSs作为测试模型的治疗策略的开发。