Shape Transformations of Lipid Bilayers Following Rapid Cholesterol Uptake

Abstract

High cholesterol levels in the blood increase the risk of atherosclerosis. A common explanation is that the cholesterol increase in the plasma membrane perturbs the shape and functions of cells by disrupting the cell signaling pathways and the formation of membrane rafts. In this work, we show that after enhanced transient uptake of cholesterol, mono-component lipid bilayers change their shape similarly to cell membranes in vivo. The bilayers either expel lipid protrusions or spread laterally as a result of the ensuing changes in their lipid density, the mechanical constraints imposed on them, and the properties of cyclodextrin used as a cholesterol donor. In light of the increasingly recognized link between membrane tension and cell behavior, we propose that the physical adaptation of the plasma membrane to cholesterol uptake may play a substantial role in the biological response.

Substrate-led cholesterol extraction from supported lipid membranes

“…Changes in lipid membranes supported on PDMS substrates Supported lipid membrane patches offer a convenient system for studying membrane-substrate interactions because they allow for simultaneous microscopic observation of the inplane membrane changes and for a quantitative analysis of the membrane surface area. 31,32 The patches can be routinely formed by fusing giant unilamellar lipid vesicles to a substrate (see Methods for further details). The substrate must be hydrophilic enough to interact with the lipid headgroups, but the interaction is usually non-specific and mediated by the thin interstitial water layer.…”

“…where χ acc (t 0 ) = χ chol (t 0 ) − χ inacc is the mole fraction of cholesterol accessible to substrate extraction, χ inacc is the mole fraction of cholesterol inaccessible to substrate extraction, and k is the depletion rate constant. Here, similarly to studies with cyclodextrin, 31,32 we neglect any asymmetry of cholesterol distribution between the membrane leaflets due to the fact that the flip-flop time of the cholesterol molecules is on the order of milliseconds, 43 orders of magnitude faster than the timescale of our experiments. Eqn (1) fits the experimental data on the changes of patch area remarkably well (Fig.…”

Macrophages Shed Excess Cholesterol in Unique Extracellular Structures Containing Cholesterol Microdomains

“…Supporting this possibility is the finding that cholesterol enrichment of supported model phospholipid bilayer membranes induces elongated lipid protrusions emanating from the bilayer. 24 , 57 , 58 The released lipid protrusions spontaneously convert to spherical structures observed by conventional fluorescence microscopy (Figure 3 A in Rahimi et al 58 ). In a similar manner, cholesterol enrichment of macrophage plasma membranes could cause shedding of cholesterol bilayer microdomains that we observed with AFM.…”

Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

“…It is well known that the vesicle shape depends on membrane curvature and bending elasticity. Several experimental results indicate that various conditions (different physical stimuli and additives) can affect the vesicle shape[71][72][73][74].Until now, a few examples have been established to evaluate the effect of a surfactant (varying in charge, length of carbon chain, structure of head group) on the properties of liposomes. There are a few examples showing that stability of cationic liposomes depends on the concentration and nature of cationic surfactants.…”