scholarly journals Cholesterol Depletion by MβCD Enhances Cell Membrane Tension and Its Variations-Reducing Integrity

2019 ◽  
Vol 116 (8) ◽  
pp. 1456-1468 ◽  
Author(s):  
Arikta Biswas ◽  
Purba Kashyap ◽  
Sanchari Datta ◽  
Titas Sengupta ◽  
Bidisha Sinha
2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Josh Childs ◽  
Zhongkui Hong Hong

Atherosclerosis remains a major cause of cardiovascular disease (CVD). Cholesterol has been identified as a major contributor to the cause of atherosclerosis. It is well known that the cholesterol accumulation in macrophage-derived foam cells is the major component of atherosclerotic plaque. However, growing evidences suggests that cholesterol loading into vascular smooth muscle cells (VSMC) in atherosclerosis is much larger than previously known, and about 40% of total foam cells in the atherosclerotic plaque are VSMC-derived. Cholesterol may not only contribute as the fatty deposition in the atherosclerotic lesion, but also play a critical role in the VSMC migration toward the intima of the blood vessel wall. In addition, the arterial wall becomes stiffer during atherosclerosis altering the micromechanical environment experienced by the VSMCs leading to changes in VSMC stiffens, adhesion, and phenotype. Migration of VSMCs is a complex process including proliferation and phenotypic switching of VSMCs, thus contributing too many changes in cell membrane adhesion molecules. We tested the hypothesis that membrane cholesterol in VSMCs may play an important role in α 5 β 1 -integrin mediated adhesion, and alter the sensory function of VSMCs to ECM mechanical properties. In this study cholesterol manipulation was achieved using methyl-β-cyclodextrin, and gel substrates with varying stiffness were used to mimic the changing environment in atherosclerosis. Atomic force microscopy (AFM) was used to determine integrin-fibronectin adhesion force and cell stiffness. A custom-written MATLAB program was used to interpret the elasticity of the VSMC cytoskeleton and adhesion force. Cellular adhesion was measured for 50%-70% confluent cells with a sample size of 50 cells on a fibronectin coated AFM stylus probe. Our results show that there is a significant decrease in α5β1-integrin adhesion of VSMCs on substrates above 9 kPa upon membrane cholesterol depletion. Additionally, mechanotransduction of VSMCs upon cholesterol depletion is less efficient. In conclusion, cell membrane cholesterol and extracellular mechanical signals may synergistically regulate cellular mechanical functions of VSMCs and their migration in the progression of atherosclerosis.


2004 ◽  
Vol 127 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Tadashi Kosawada ◽  
Kohji Inoue ◽  
Geert W. Schmid-Schönbein

Highly curved cell membrane structures, such as plasmalemmal vesicles (caveolae) and clathrin-coated pits, facilitate many cell functions, including the clustering of membrane receptors and transport of specific extracellular macromolecules by endothelial cells. These structures are subject to large mechanical deformations when the plasma membrane is stretched and subject to a change of its curvature. To enhance our understanding of plasmalemmal vesicles we need to improve the understanding of the mechanics in regions of high membrane curvatures. We examine here, theoretically, the shapes of plasmalemmal vesicles assuming that they consist of three membrane domains: an inner domain with high curvature, an outer domain with moderate curvature, and an outermost flat domain, all in the unstressed state. We assume the membrane properties are the same in these domains with membrane bending elasticity as well as in-plane shear elasticity. Special emphasis is placed on the effects of membrane curvature and in-plane shear elasticity on the mechanics of vesicle during unfolding by application of membrane tension. The vesicle shapes were computed by minimization of bending and in-plane shear strain energy. Mechanically stable vesicles were identified with characteristic membrane necks. Upon stretch of the membrane, the vesicle necks disappeared relatively abruptly leading to membrane shapes that consist of curved indentations. While the resting shape of vesicles is predominantly affected by the membrane spontaneous curvatures, the membrane shear elasticity (for a range of values recorded in the red cell membrane) makes a significant contribution as the vesicle is subject to stretch and unfolding. The membrane tension required to unfold the vesicle is sensitive with respect to its shape, especially as the vesicle becomes fully unfolded and approaches a relative flat shape.


2009 ◽  
Vol 106 (29) ◽  
pp. 11972-11977 ◽  
Author(s):  
R. Nambiar ◽  
R. E. McConnell ◽  
M. J. Tyska

2000 ◽  
Vol 11 (12) ◽  
pp. 4339-4346 ◽  
Author(s):  
Tatsuru Togo ◽  
Tatiana B. Krasieva ◽  
Richard A. Steinhardt

We hypothesized that the requirement for Ca2+-dependent exocytosis in cell-membrane repair is to provide an adequate lowering of membrane tension to permit membrane resealing. We used laser tweezers to form membrane tethers and measured the force of those tethers to estimate the membrane tension of Swiss 3T3 fibroblasts after membrane disruption and during resealing. These measurements show that, for fibroblasts wounded in normal Ca2+ Ringer's solution, the membrane tension decreased dramatically after the wounding and resealing coincided with a decrease of ∼60% of control tether force values. However, the tension did not decrease if cells were wounded in a low Ca2+ Ringer's solution that inhibited both membrane resealing and exocytosis. When cells were wounded twice in normal Ca2+ Ringer's solution, decreases in tension at the second wound were 2.3 times faster than at the first wound, correlating well with twofold faster resealing rates for repeated wounds. The facilitated resealing to a second wound requires a new vesicle pool, which is generated via a protein kinase C (PKC)-dependent and brefeldin A (BFA)-sensitive process. Tension decrease at the second wound was slowed or inhibited by PKC inhibitor or BFA. Lowering membrane tension by cytochalasin D treatment could substitute for exocytosis and could restore membrane resealing in low Ca2+ Ringer's solution.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Tomáš Venit ◽  
Alžběta Kalendová ◽  
Martin Petr ◽  
Rastislav Dzijak ◽  
Lukáš Pastorek ◽  
...  

Soft Matter ◽  
2015 ◽  
Vol 11 (6) ◽  
pp. 1107-1115 ◽  
Author(s):  
Xin Yi ◽  
Huajian Gao

A theoretical study on cell membrane wrapping of a spherical thin elastic shell indicates that stiff nanocapsules achieve full wrapping easier than soft ones. The detailed analysis demonstrates how the wrapping degree depends on the size and stiffness of the nanocapsules, adhesion energy and membrane tension.


2021 ◽  
Author(s):  
Eva Kreysing ◽  
Jeffrey Mc Hugh ◽  
Sarah K. Foster ◽  
Kurt Andresen ◽  
Ryan D. Greenhalgh ◽  
...  

Most animal cells are surrounded by a cell membrane and an underlying actomyosin cortex. Both structures are linked with each other, and they are under tension. Membrane tension and cortical tension both influence many cellular processes, including cell migration, division, and endocytosis. However, while actomyosin tension is regulated by substrate stiffness, how membrane tension responds to mechanical substrate properties is currently poorly understood. Here, we probed the effective membrane tension of neurons and fibroblasts cultured on glass and polyacrylamide substrates of varying stiffness using optical tweezers. In contrast to actomyosin-based traction forces, both peak forces and steady state tether forces of cells cultured on hydrogels were independent of substrate stiffness and did not change after blocking myosin II activity using blebbistatin, indicating that tether and traction forces are not directly linked with each other. Peak forces on hydrogels were about twice as high in fibroblasts if compared to neurons, indicating stronger membrane-cortex adhesion in fibroblasts. Finally, tether forces were generally higher in cells cultured on hydrogels compared to cells cultured on glass, which we attribute to substrate-dependent alterations of the actomyosin cortex and an inverse relationship between tension along stress fibres and cortical tension. Our results provide new insights into the complex regulation of membrane tension, and they pave the way for a deeper understanding of biological processes instructed by it.


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