Label-Free Imaging of Cholesterol Assemblies Reveals Hidden Nanomechanics of Breast Cancer Cells.
Label-Free Imaging of Cholesterol Assemblies Reveals Hidden Nanomechanics of Breast Cancer Cells.
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DOI：
10.1002/advs.202002643
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Alsteens D
中科院分区：
文献类型：
--
作者：
Dumitru AC;Mohammed D;Maja M;Yang J;Verstraeten S;Del Campo A;Mingeot-Leclercq MP;Tyteca D;Alsteens D
肿瘤细胞在其组成、结构组织和功能特性方面存在深刻的变化。癌细胞的一个里程碑是整体改变的机械表型，到目前为止，这与其细胞骨架调节和组织的变化有关。有证据表明，癌细胞的质膜（PM）也显示出其组成和组织的剧烈变化。然而，PM的生物力学表征仍然有限，主要是由于难以以定量和无标签的方式对其进行研究。在这里，一系列的MCF 10细胞系，作为乳腺癌进展的模型，PM的生物力学性能进行了研究。值得注意的是，观察到细胞PM弹性和肿瘤发生之间的强相关性。如PM相关胆固醇水平所强调的，癌症进展下改变的膜组成导致PM变硬，其与弹性细胞骨架特性解偶联。相反，转移性细胞的胆固醇消耗导致其PM软化，恢复类似于良性细胞的生物力学特性。由于基于靶向癌细胞膜脂质的新型疗法代表了抗癌药物开发领域中一种有前途的方法，因此该方法有助于破译PM脂质含量与疾病之间的功能联系。在这里，侵袭性恶性乳腺癌细胞被证明比健康和癌前病变的细胞更柔软，并且具有增加的质膜胆固醇含量，增加其张力和刚度，这是介导细胞反应的关键参数。
Tumor cells present profound alterations in their composition, structural organization, and functional properties. A landmark of cancer cells is an overall altered mechanical phenotype, which so far are linked to changes in their cytoskeletal regulation and organization. Evidence exists that the plasma membrane (PM) of cancer cells also shows drastic changes in its composition and organization. However, biomechanical characterization of PM remains limited mainly due to the difficulties encountered to investigate it in a quantitative and label‐free manner. Here, the biomechanical properties of PM of a series of MCF10 cell lines, used as a model of breast cancer progression, are investigated. Notably, a strong correlation between the cell PM elasticity and oncogenesis is observed. The altered membrane composition under cancer progression, as emphasized by the PM‐associated cholesterol levels, leads to a stiffening of the PM that is uncoupled from the elastic cytoskeletal properties. Conversely, cholesterol depletion of metastatic cells leads to a softening of their PM, restoring biomechanical properties similar to benign cells. As novel therapies based on targeting membrane lipids in cancer cells represent a promising approach in the field of anticancer drug development, this method contributes to deciphering the functional link between PM lipid content and disease. Here, invasive malignant breast cancer cells are demonstrated to be softer than their healthy and premalignant counterparts and have an increased plasma membrane cholesterol content, increasing its tension and stiffness, which are critical parameters in the mediation of cellular responses.
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影响因子：
19.6
作者：
Han, Yu Long;Pegoraro, Adrian F.;Guo, Ming
通讯作者：
Guo, Ming
影响因子：
17.1
作者：
Guerrero, Carlos R.;Garcia, Pablo D.;Garcia, Ricardo
通讯作者：
Garcia, Ricardo
DOI：
10.1083/jcb.201701039
发表时间：
2018-05-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Broders-Bondon F;Nguyen Ho-Bouldoires TH;Fernandez-Sanchez ME;Farge E
通讯作者：
Farge E
影响因子：
1.6
作者：
Hermanowicz, Pawel;Sarna, Michal;Gabrys, Halina
通讯作者：
Gabrys, Halina
影响因子：
8
作者：
Carquin, Melanie;Conrard, Louise;Tyteca, Donatienne
通讯作者：
Tyteca, Donatienne