Cell membrane softening in human breast and cervical cancer cells

Händel, Chris; Schmidt, Betina; Schiller, Jürgen; Dietrich, U.; Möhn, Till; Kießling, T.; Pawlizak, Steve; Fritsch, Anatol; Horn, Lars‐Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

doi:10.1088/1367-2630/17/8/083008

Cited by 39 publications

(38 citation statements)

References 47 publications

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“…Furthermore, we have demonstrated that the uptake pathway can be influenced by treatment of the cells with liposomes. Our key finding that softness/stiffness of lipid bilayers can modulate dynamin dependency, when juxtaposed with a recent report that epithelial tumor cells such as MDA‐MB‐231 are softer than their healthy counterparts suggests that localized priming of the tumors with liposomes could be exploited to modulate biophysical interactions between nanomedicine and cell membrane to increase the efficiency of polymeric NP‐based therapies through GTP‐dependent pathways.…”

Section: Resultssupporting

confidence: 59%

Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness

Xiang

Sarem

Shah

et al. 2018

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Nanomedicines can be taken up by cells via nonspecific and dynamin-dependent (energy-dependent) clathrin and caveolae-mediated endocytosis. While significant effort has focused on targeting pathway-specific transporters, the role of nanobiophysics in the cell lipid bilayer nanoparticle uptake pathway remains largely unexplored. In this study, it is demonstrated that stiffness of lipid bilayer is a key determinant of uptake of liposomes by mammalian cells. Dynamin-mediated endocytosis (DME) of liposomes is found to correlate with its phase behavior, with transition toward solid phase promoting DME, and transition toward fluidic phase resulting in dynamin-independent endocytosis. Since liposomes can transfer lipids to cell membrane, it is sought to engineer the biophysical properties of the membrane of breast epithelial tumor cells (MD-MBA-231) by treatment with phosphatidylcholine liposomes, and elucidate its effect on the uptake of polymeric nanoparticles. Analysis of the giant plasma membrane vesicles derived from treated cells using flicker spectroscopy reveals that liposome treatment alters membrane stiffness and DME of nanoparticles. Since liposomes have a history of use in drug delivery, localized priming of tumors with liposomes may present a hitherto unexploited means of targeting tumors based on biophysical interactions.

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Section: Resultssupporting

confidence: 59%

Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness

Xiang

Sarem

Shah

et al. 2018

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“…Our statement that lower membrane rigidity correlates with higher migration potential is supported by a study about primary cancer cells isolated from human patients [47]. Primary cancer cells contain higher levels of phospholipids with shorter fatty acid chain length than non-malignant primary samples, resulting in softening of the cell membrane.…”

Section: Discussionsupporting

confidence: 61%

Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion

et al. 2015

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The invasive potential of cancer cells strongly depends on cellular stiffness, a physical quantity that is not only regulated by the mechanical impact of the cytoskeleton but also influenced by the membrane rigidity. To analyze the specific role of membrane rigidity in cancer progression, we treated cancer cells with the Acetyl-CoA carboxylase inhibitor Soraphen A and revealed an alteration of the phospholipidome via mass spectrometry. Migration, invasion, and cell death assays were employed to relate this alteration to functional consequences, and a decrease of migration and invasion without significant impact on cell death has been recorded. Fourier fluctuation analysis of giant plasma membrane vesicles showed that Soraphen A increases membrane rigidity of carcinoma cell membranes. Mechanical measurements of the creep deformation response of whole intact cells were performed using the optical stretcher. The increase in membrane rigidity was observed in one cell line without changing the creep deformation response indicating no restructuring of the cytoskeleton. These data indicate that the increase of membrane rigidity alone is sufficient to inhibit invasiveness of cancer cells, thus disclosing the eminent role of membrane rigidity in migratory processes.

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“…Supposing that fluctuations are of thermal origin, larger fluctuations indicate a lower rigidity in the highly metastatic cells. Softening of the plasma membrane was also reported recently in breast and cervical cancer cells using fluctuation analysis of membrane blebs or of giant plasma membrane vesicles (Händel et al., ). Conversely a pharmacological inhibitor that increases membrane rigidity also decreases invasiveness of a mammary carcinoma cell line (Braig et al., ).…”

Section: Why Are Cancer Cells Softer Than Normal Cells?supporting

confidence: 56%

Are cancer cells really softer than normal cells?

Charlotte

Goud

Manneville

2017

Biology of the Cell

267

236

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Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression.

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Cell membrane softening in human breast and cervical cancer cells

Cited by 39 publications

References 47 publications

Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness

Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness

Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion

Are cancer cells really softer than normal cells?

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