Laboratory for Multiscale Mechanics and Medical Science, Department of Engineering Mechanics, SVL, School of Aerospace Engineering, Xi'an Jiaotong University, Xi'an 710049, China.
Laboratory for Multiscale Mechanics and Medical Science, Department of Engineering Mechanics, SVL, School of Aerospace Engineering, Xi'an Jiaotong University, Xi'an 710049, China.
Acta Biomater. 2024 May;180:197-205. doi: 10.1016/j.actbio.2024.04.002. Epub 2024 Apr 9.
During physiological and pathological processes, cells experience significant morphological alterations with the re-arrangement of cytoskeletal filaments, resulting in anisotropic viscoelasticity. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. We investigate how cell shape affects its creep responses in longitudinal and perpendicular directions. It is shown that cells exhibit power-law rheological behavior in both longitudinal and perpendicular directions under step stress, with a more solid-like behavior along the longitudinal direction. We reveal that the cell volume and cytoskeletal filament orientation, which have been neglected in most existing models, play a critical role in regulating cellular anisotropic viscoelasticity. The stiffness of the cell in both directions increases linearly with increasing its aspect ratio, due to the decrease of cell volume. Moreover, the increase in the cell's aspect ratio produces the aggregation of cytoskeletal filaments along the longitudinal direction, resulting in higher stiffness in this direction. It is also shown that the increase in cell's aspect ratio corresponds to a process of cellular ordering, which can be quantitatively characterized by the orientational entropy of cytoskeletal filaments. In addition, we present a simple yet robust method to establish the relationship between cell's aspect ratio and cell volume, thus providing a theoretical framework to capture the anisotropic viscoelastic behavior of cells. This study suggests that the structure-based cell models may be further developed to investigate cellular rheological responses to external mechanical stimuli and may be extended to the tissue scale. STATEMENT OF SIGNIFICANCE: The viscoelastic behaviors of cells hold significant importance in comprehending the roles of mechanical forces in embryo development, invasion, and metastasis of cancer cells. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. Our study highlights the crucial role of previously neglected factors, such as cell volume and cytoskeletal filament orientation, in regulating cellular anisotropic viscoelasticity. We further propose an orientational entropy of cytoskeletal filaments to quantitatively characterize the ordering process of cells with increasing aspect ratios. Moreover, we derived the analytical interrelationships between cell aspect ratio, cell stiffness, cell volume, and cytoskeletal fiber orientation. This study provides a theoretical framework to describe the anisotropic viscoelastic mechanical behavior of cells.
在生理和病理过程中，细胞经历细胞骨架丝的重新排列，导致各向异性粘弹性的显著形态改变。在这里，提出了一种基于结构的细胞模型来研究活细胞的各向异性粘弹性力学行为。我们研究了细胞形状如何影响其在纵向和垂直方向上的蠕变响应。结果表明，在阶跃应力下，细胞在纵向和垂直方向上均表现出幂律流变行为，沿纵向表现出更固体状的行为。我们揭示了细胞体积和细胞骨架丝取向，这在大多数现有模型中被忽略，在调节细胞各向异性粘弹性方面起着关键作用。由于细胞体积的减小，细胞在两个方向上的刚度均随其纵横比的增加呈线性增加。此外，细胞纵横比的增加会导致细胞骨架丝沿纵向聚集，从而导致该方向的刚度增加。结果还表明，细胞纵横比的增加对应于细胞有序化的过程，这可以通过细胞骨架丝的取向熵来定量描述。此外，我们提出了一种简单而强大的方法来建立细胞纵横比与细胞体积之间的关系，从而为捕获细胞的各向异性粘弹性行为提供了理论框架。本研究表明，基于结构的细胞模型可以进一步发展，以研究细胞对外界机械刺激的流变响应，并可以扩展到组织尺度。
细胞的粘弹性行为对于理解机械力在胚胎发育、癌细胞浸润和转移中的作用具有重要意义。在这里，提出了一种基于结构的细胞模型来研究活细胞的各向异性粘弹性力学行为。我们的研究强调了以前被忽视的因素，如细胞体积和细胞骨架丝取向，在调节细胞各向异性粘弹性中的关键作用。我们进一步提出了细胞骨架丝的取向熵，以定量描述纵横比增加的细胞的有序化过程。此外，我们推导出了细胞纵横比、细胞刚度、细胞体积和细胞骨架纤维取向之间的解析相互关系。本研究为描述细胞的各向异性粘弹性力学行为提供了理论框架。
