简单剪切流中细胞球的形态
The morphology of cell spheroids in simple shear flow
AI总结：
针对明确定义流场对细胞球影响的研究空白，提出在平行板装置中施加简单剪切流并结合显微成像观察的技术，发现细胞球刚性旋转、外层细胞脱落且尺寸减小速率与剪切应力正相关，可用于估算细胞间黏附力，为力学生物学研究提供定量方法。
摘要：
细胞球是体外研究三维微环境中细胞-细胞及细胞-基质相互作用的常用模型。目前多数细胞球研究聚焦于静态条件下其对各类刺激的响应。近年来，已有研究围绕间质空间中的肿瘤侵袭问题，探究了流动对细胞球的影响。具体而言，已有实验证实，对包埋在胶原蛋白基质中的细胞球进行微流控灌注，可调节细胞间黏附，且代表了间质流促进肿瘤侵袭的一种可能机制。但现有文献仍缺乏关于明确定义的流场对细胞球影响的研究。本研究在平行板装置中对细胞球施加简单剪切流，同时通过光学显微镜观察其形态变化。借助图像分析技术，我们发现细胞球在流动中如同刚性颗粒一般旋转。随着时间推移，细胞球外层的细胞从受剪切的细胞球上脱落，并被流动带走。因此，细胞球的尺寸随时间减小，且减小速率随外部剪切应力的增大而提升，该特性可用于估算细胞间黏附力。本工作提出的技术能够在成熟的剪切流场中，将流动诱导的效应与细胞球的显微成像相关联，从而为获取力学生物学通用领域相关的定量结果提供了一种方法。
英文摘要：
Cell spheroids are a widely used model to investigate cell-cell and cell-matrix interactions in a 3D microenvironment in vitro. Most research on cell spheroids has been focused on their response to various stimuli under static conditions. Recently, the effect of flow on cell spheroids has been investigated in the context of tumor invasion in interstitial space. In particular, microfluidic perfusion of cell spheroids embedded in a collagen matrix has been shown to modulate cell-cell adhesion and to represent a possible mechanism promoting tumor invasion by interstitial flow. However, studies on the effects of well-defined flow fields on cell spheroids are lacking in the literature. Here, we apply simple shear flow to cell spheroids in a parallel plate apparatus while observing their morphology by optical microscopy. By using image analysis techniques, we show that cell spheroids rotate under flow as rigid particles. As time goes on, cells from the outer layer detach from the sheared cell spheroids and are carried away by the flow. Hence, the size of cell spheroids declines with time at a rate increasing with the external shear stress, which can be used to estimate cell-cell adhesion. The technique proposed in this work allows one to correlate flow-induced effects with microscopy imaging of cell spheroids in a well-established shear flow field, thus providing a method to obtain quantitative results which are relevant in the general field of mechanobiology.
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