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.
Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.
Oral rehydration solutions (ORS) are a simple and cheap method to treat diarrheal dehydration and acidosis. To maintain the energy supply of diarrheic calves, it is necessary to continue milk feeding. Suckling of milk or milk-based or hypertonic water-based ORS produces a slower rate of abomasal emptying than suckling isotonic water-based ORS. The faster abomasal passage of isotonic water-based ORS implies that efficacious electrolytes reach the gut more quickly, possibly providing a faster rate of rehydration. The aim of the study was to verify when and to what extent milk and water- and milk-based ORS increase plasma volume and affect plasma osmolality and acid-base status in healthy suckling calves. Eleven calves were fed with milk and with an ORS that was prepared in water or milk. Moreover, for one experiment, the calves remained fasting without suckling milk or ORS. During the experimental phase, the calves were deprived of water, hay, and concentrates. Blood samples were taken before and at various time points after feeding. Total plasma protein, osmolality, [Na(+)], [K(+)], [Cl(-)], and albumin were determined. In 6 of 11 experiments, blood gas analysis was also performed. The calculated change in plasma volume after feeding was assessed from the plasma protein concentration before feeding (P(t=0)) and the plasma protein concentration after feeding (P(t=x)): (P(t=0)- P(t=x)) × 100/P(t=x). Water- and milk-based ORS produced equal rates of plasma expansion in healthy calves. After milk feeding, the change in plasma volume was decelerated. Because of water influx, we did not observe a significant effect of feeding regimen on plasma osmolality. Acid-base status was little affected by feeding regimen. Feeding of milk-based ORS increased plasma strong ion difference, an alkaline response, which could potentially also reduce acidosis in calves suffering from diarrhea.
Modeling approaches of suspended, rod-like particles and recent experimental data have shown that depletion forces display different signatures depending on the orientation of these particles. It has been shown that axial attraction of two rods yields contractile forces of 0.1 pN that are independent of the relative axial shift of the two rods. Here, we measured depletion-caused interactions of actin bundles extending the phase space of single pairs of rods to a multi-particle system. In contrast to a filament pair, we found forces up to 3 pN. Upon bundle relaxation forces decayed exponentially with a mean decay time of 3.4 s. These different dynamics are explained within the frame of a mathematical model by taking pairwise interactions to a multi-filament scale. The macromolecular content employed for our experiments is well below the crowding of cells. Thus, we propose that arising forces can contribute to biological force generation without the need to convert chemical energy into mechanical work.
Background: Cellular heterogeneity in tumor cells is a well-established phenomenon. Genetic and phenotypic cell-to-cell variability have been observed in numerous studies both within the same type of cancer cells and across different types of cancers. Another known fact for metastatic tumor cells is that they tend to be softer than their normal or non-metastatic counterparts. However, the heterogeneity of mechanical properties in tumor cells are not widely studied. Results: Here we analyzed single-cell optical stretcher data with machine learning algorithms on three different breast tumor cell lines and show that similar heterogeneity can also be seen in mechanical properties of cells both within and between breast tumor cell lines. We identified two clusters within MDA-MB-231 cells, with cells in one cluster being softer than in the other. In addition, we show that MDA-MB-231 cells and MDA-MB-436 cells which are both epithelial breast cancer cell lines with a mesenchymal-like phenotype derived from metastatic cancers are mechanically more different from each other than from non-malignant epithelial MCF-10A cells. Conclusion: Since stiffness of tumor cells can be an indicator of metastatic potential, this result suggests that metastatic abilities could vary within the same monoclonal tumor cell line.
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