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.

中文翻译：

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胆固醇组件的无标记成像揭示了乳腺癌细胞隐藏的纳米力学

肿瘤细胞的组成、结构组织和功能特性发生了深刻的改变。癌细胞的一个里程碑是机械表型的整体改变，迄今为止，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) 的组成和组织也发生了巨大的变化。然而，PM 的生物力学表征仍然有限，主要是因为以定量和无标记的方式研究它遇到困难。在此，研究了用作乳腺癌进展模型的一系列 MCF10 细胞系的 PM 的生物力学特性。值得注意的是，观察到细胞 PM 弹性与肿瘤发生之间存在很强的相关性。正如 PM 相关胆固醇水平所强​​调的那样，癌症进展过程中膜成分的改变导致 PM 变硬，这与弹性细胞骨架特性无关。相反，转移细胞的胆固醇消耗导致其 PM 软化，恢复与良性细胞相似的生物力学特性。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的一种有前途的方法，该方法有助于破译 PM 脂质含量与疾病之间的功能联系。