Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments.
Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments.
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DOI：
10.1038/s41598-021-85640-5
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发表时间：
2021-03-22
影响因子：
4.6
通讯作者：
Mak M
中科院分区：
文献类型：
--
作者：
Zhang X;Chan T;Mak M
癌细胞转移是癌症相关死亡的一个主要因素。在转移过程中，癌细胞呈现迁移表型，并穿过致密细胞外基质中的孔隙进行侵袭。然而，对于具有相似迁移表型的细胞的形态和亚细胞特征以及几何限制对细胞形态动力学的影响，人们还知之甚少。在此，我们研究了在受限微环境中，高侵袭性的MDA - MB - 231细胞以单细胞和细胞对（一种初始且简化的群体状态）形式存在时的表型。我们对表型相似的单细胞和细胞对进行分组，并对相关的形态和亚细胞特征进行描述。我们进一步在快速迁移的单细胞组内检测到两种不同的迁移表型，即波动型和非波动型。此外，我们证明了细胞在穿过几何限制进行侵袭后，其前沿形成的突起数量增加。最后，我们追踪了不同程度的限制对突起形成的短期和长期影响。总体而言，我们的研究结果阐明了与不同单细胞和细胞对表型相关的潜在形态和亚细胞特征，以及穿过受限几何结构侵袭对细胞行为的影响。
Cancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.
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影响因子：
16.6
作者：
Zanotelli, Matthew R.;Rahman-Zaman, Aniqua;Reinhart-King, Cynthia A.
通讯作者：
Reinhart-King, Cynthia A.
影响因子：
4.6
作者：
Pal-Ghosh, Sonali;Tadvalkar, Gauri;Stepp, Mary Ann
通讯作者：
Stepp, Mary Ann
影响因子：
4.7
作者：
Yokota, J
通讯作者：
Yokota, J
影响因子：
7.5
作者：
Jacquemet, Guillaume;Hamidi, Hellyeh;Ivaska, Johanna
通讯作者：
Ivaska, Johanna
影响因子：
64.8
作者：
Vasan N;Baselga J;Hyman DM
通讯作者：
Hyman DM