Soft Matter Physics Division, Peter Debye Institute for Soft Matter Physics, University of Leipzig, Germany.
Department of Physics, Northeastern University, Boston, MA 02115, USA.
Soft Matter. 2024 Feb 28;20(9):1996-2007. doi: 10.1039/d3sm00630a.
In cell clusters, the prominent factors at play encompass contractility-based enhanced tissue surface tension and cell unjamming transition. The former effect pertains to the boundary effect, while the latter constitutes a bulk effect. Both effects share outcomes of inducing significant elongation in cells. This elongation is so substantial that it surpasses the limits of linear elasticity, thereby giving rise to additional effects. To investigate these effects, we employ atomic force microscopy (AFM) to analyze how the mechanical properties of individual cells change under such considerable elongation. Our selection of cell lines includes MCF-10A, chosen for its pronounced demonstration of the extended differential adhesion hypothesis (eDAH), and MDA-MB-436, selected due to its manifestation of cell unjamming behavior. In the AFM analyses, we observe a common trend in both cases: as elongation increases, both cell lines exhibit strain stiffening. Notably, this effect is more prominent in MCF-10A compared to MDA-MB-436. Subsequently, we employ AFM on a dynamic range of 1-200 Hz to probe the mechanical characteristics of cell spheroids, focusing on both surface and bulk mechanics. Our findings align with the results from single cell investigations. Specifically, MCF-10A cells, characterized by strong contractile tissue tension, exhibit the greatest stiffness on their surface. Conversely, MDA-MB-436 cells, which experience significant elongation, showcase their highest stiffness within the bulk region. Consequently, the concept of single cell strain stiffening emerges as a crucial element in understanding the mechanics of multicellular spheroids (MCSs), even in the case of MDA-MB-436 cells, which are comparatively softer in nature.
在细胞簇中，起主要作用的因素包括基于收缩性的增强组织表面张力和细胞解聚集转变。前者与边界效应有关，而后者构成体相效应。这两种效应都导致细胞发生显著伸长。这种伸长非常显著，超过了线性弹性的限制，从而产生了其他效应。为了研究这些效应，我们使用原子力显微镜（AFM）来分析在如此大的伸长下单个细胞的机械性能如何变化。我们选择的细胞系包括 MCF-10A，因其明显表现出扩展的差异粘附假说（eDAH），以及 MDA-MB-436，因其表现出细胞解聚集行为。在 AFM 分析中，我们观察到这两种情况下的一个共同趋势：随着伸长的增加，两种细胞系都表现出应变硬化。值得注意的是，与 MDA-MB-436 相比，这种效应在 MCF-10A 中更为显著。随后，我们在 1-200Hz 的动态范围内使用 AFM 探测细胞球体的机械特性，重点关注表面和体相力学。我们的发现与单细胞研究的结果一致。具体来说，具有较强组织张力的 MCF-10A 细胞在其表面表现出最大的刚度。相反，经历显著伸长的 MDA-MB-436 细胞在体相区域表现出最高的刚度。因此，单细胞应变硬化的概念成为理解多细胞球体（MCS）力学的关键因素，即使在 MDA-MB-436 细胞这种性质上相对较软的细胞中也是如此。
