Label‐Free Imaging of Cholesterol Assemblies Reveals Hidden Nanomechanics of Breast Cancer Cells. Issue 22 (8th October 2020)

• Record Type: Journal Article
• Authors: Dumitru, Andra C.; Mohammed, Danahe; Maja, Mauriane; Yang, Jinsung; Verstraeten, Sandrine; del Campo, Aranzazu; Mingeot‐Leclercq, Marie‐Paule; Tyteca, Donatienne; Alsteens, David
• Is Part Of: Advanced science. Volume 7:Issue 22(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-08
• Subjects: atomic force microscopy -- cancer cells -- cell mechanics -- cholesterol -- plasma membrane; Science -- Periodicals; 505
• DOI: 10.1002/advs.202002643
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : 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.