由于细胞弹性的时间波动，细胞集合体的机械不均匀性增强
Enhanced mechanical heterogeneity of cell collectives due to temporal fluctuations in cell elasticity
摘要：
细胞是动态系统，其特征在于生物物理性质如刚度和收缩性的时间变化。最近的研究表明，肌动蛋白丝在细胞皮层（细胞膜下的蛋白质网络）中的招募和释放导致细胞在分裂前变硬，分裂后立即变软。在三维（3D）的细胞集体，目前还不清楚是否在单细胞规模的分裂过程中的刚度变化控制的空间结构和动力学在多细胞规模。这是一个需要理解的重要问题，因为细胞刚度变化在组织空间组织和癌症进展中起着重要作用。使用一个最小的三维模型，结合细胞的出生，死亡，细胞与细胞的弹性和粘附力的相互作用，我们调查的机械异质性的影响-在个别细胞刚度的变化，使肿瘤细胞的集体-肿瘤的空间组织和细胞动力学。我们发现，空间力学异质性的特点是一个球体核心组成的较硬的细胞和较软的细胞在周边出现在密集的三维细胞集体，这可能是一个多细胞肿瘤生长的一般特征。我们发现，提高空间力学异质性增强单细胞动力学和体积肿瘤生长的细胞弹性波动驱动。我们的研究结果可能对理解单细胞刚度的时空变化如何决定肿瘤的生长和扩散具有重要意义。
英文摘要：
Cells are dynamic systems characterized by temporal variations in biophysical properties such as stiffness and contractility. Recent studies show that the recruitment and release of actin filaments into and out of the cell cortex - a network of proteins underneath the cell membrane - leads to cell stiffening prior to division and softening immediately afterward. In three-dimensional (3D) cell collectives, it is unclear whether the stiffness change during division at the single-cell scale controls the spatial structure and dynamics at the multicellular scale. This is an important question to understand as cell stiffness variations play an important role in tissue spatial organization and cancer progression. Using a minimal 3D model incorporating cell birth, death, and cell-to-cell elastic and adhesive interactions, we investigate the effect of mechanical heterogeneity - variations in individual cell stiffnesses that make up the tumor cell collective - on tumor spatial organization and cell dynamics. We discover that spatial mechanical heterogeneity characterized by a spheroid core composed of stiffer cells and softer cells in the periphery emerge within dense 3D cell collectives, which may be a general feature of multicellular tumor growth. We show that heightened spatial mechanical heterogeneity enhances single-cell dynamics and volumetric tumor growth driven by fluctuations in cell elasticity. Our results could have important implications for understanding how spatiotemporal variations in single-cell stiffness determine tumor growth and spread.
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