01 March 2017 by Irena Levitan

Paradoxical impact of cholesterol on lipid packing and cell stiffness

Cell stiffness or deformability is a fundamental property that is expected to play a major role in multiple cellular functions. It is well known that cell stiffness is dominated by the intracellular cytoskeleton that together with the plasma membrane forms a membrane-cytoskeleton envelope. However, our understanding of how lipid composition of plasma membrane regulates physical properties of the underlying cytoskeleton is only starting to emerge. Cholesterol is one of the major lipid components of the plasma membrane in all mammalian cells and its impact on the physical properties of the membrane lipid bilayer is well studied, both in pure lipid environments, such as liposomes or lipid monolayers, and in cellular membranes. Our studies demonstrate, however, that an increase in the rigidity and lipid packing of the bilayer does not translate into an increase in the overall stiffness of the cellular envelope, a bi-component system where the sub-membrane cytoskeleton underlies the membrane lipid bilayer. In contrast, it appears that there is an inverse relationship between the lipid order of the membrane bilayer and the stiffness of the cellular envelope that is dominated by the cortical cytoskeleton. First, we showed that cholesterol depletion results in significant stiffening and loss of deformability of vascular endothelial cells by measuring progressive membrane deformation in response to negative pressure applied by a glass micropipette. These data were verified by measuring endothelial elastic modulus using Atomic Force Microscopy. Furthermore, using a combination of experimental and computational techniques, we show that incorporation of oxysterols and other oxidized lipids into endothelial membranes that disrupt lipid packing result significant increase in endothelial elastic modulus and increase in endothelial force generation. In contrast, loading the cells with cholesterol rescue all the effects described above.

About the author

profile picture of Irena Levitan

Irena Levitan

United States

Key Contributors

Tzu-Pin Shentu, Myung-Jin Oh, Elizabeth LeMaster, Manuela A. Ayee and Irena Levitan Division of Pulmonary Care, Department of Medicine, University of Illinois at Chicago

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