Strain-dependent elastography of cancer cells reveals heterogeneity and stiffening due to attachment
Strain-dependent elastography of cancer cells reveals heterogeneity and stiffening due to attachment
复制标题
癌细胞的应变依赖性弹性成像揭示了由于附着而产生的异质性和硬化
DOI：
10.1016/j.jbiomech.2023.111479
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发表时间：
2023
影响因子：
2.4
通讯作者：
Sulchek, Todd
中科院分区：
文献类型：
--
作者：
Xu, Wenwei;Kabariti, Saif;Young, Katherine M.;Swingle, Steven P.;Liu, Alan Y.;Sulchek, Todd
由于细胞的厚度和生物力学特性各不相同，因此在原子力显微镜 (AFM) 刚度映射过程中使用恒力触发器会产生不同的标称应变，从而使局部材料特性的比较变得混乱。在这项研究中，我们通过使用压痕依赖性逐点赫兹方法测量了卵巢癌细胞和乳腺癌细胞的生物力学空间异质性。力曲线和表面形貌一起用来确定细胞刚度作为标称应变的函数。通过记录特定应变下的刚度，可以改善细胞材料特性的比较，并产生细胞机械特性的更高对比度表示。定义对应于适度标称应变的线性弹性区域，我们能够清楚地区分细胞核周区域的力学。我们观察到，相对于片状足的硬度，转移性癌细胞的核周区域比非转移性癌细胞更软。此外，应变依赖性弹性成像与赫兹模型分析的传统力映射的对比揭示了薄片状足区域中的显着硬化现象，其中模量与细胞厚度成反比且呈指数比例缩放。观察到的指数硬化不受细胞骨架张力松弛的影响，但有限元模型表明它受到基材粘附的影响。这种新颖的细胞图谱技术探索了由区域异质性引起的癌细胞机械非线性，这有助于解释转移性癌细胞如何表现出软表型，同时增加力的产生和侵袭性。
Because cells vary in thickness and in biomechanical properties, the use of a constant force trigger during atomic force microscopy (AFM) stiffness mapping produces a varied nominal strain that can obfuscate the comparison of local material properties. In this study, we measured the biomechanical spatial heterogeneity of ovarian and breast cancer cells by using an indentation-dependent pointwise Hertzian method. Force curves and surface topography were used together to determine cell stiffness as a function of nominal strain. By recording stiffness at a particular strain, it may be possible to improve comparison of the material properties of cells and produce higher contrast representations of cell mechanical properties. Defining a linear region of elasticity that corresponds to a modest nominal strain, we were able to clearly distinguish the mechanics of the perinuclear region of cells. We observed that, relative to the lamelopodial stiffness, the perinuclear region was softer for metastatic cancer cells than their nonmetastatic counterparts. Moreover, contrast in the strain-dependent elastography in comparison to conventional force mapping with Hertzian model analysis revealed a significant stiffening phenomenon in the thin lamellipodial region in which the modulus scales inversely and exponentially with cell thickness. The observed exponential stiffening is not affected by relaxation of cytoskeletal tension, but finite element modeling indicates it is affected by substrate adhesion. The novel cell mapping technique explores cancer cell mechanical nonlinearity that results from regional heterogeneity, which could help explain how metastatic cancer cells can show soft phenotypes while simultaneously increasing force generation and invasiveness.