Lysolipids regulate raft size distribution

Abstract

The lipid matrix of cellular membranes, directly and indirectly, regulates many vital functions of the cell. The diversity of lipids in membranes leads to the formation of ordered domains called rafts, which play a crucial role in signal transduction, protein sorting and other cellular processes. Rafts are believed to impact the development of different neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s ones, amyotrophic lateral sclerosis, some types of cancer, etc. These diseases correlate with the change in the membrane lipid composition resulting from an oxidative stress, age-related processes, dysfunction of proteins, and many others. In particular, a lot of studies report a significant rise in the level of lysolipids. Physicochemical properties of rafts are determined by membrane composition, in particular, by the content of lysolipids. Lysolipids may thus regulate raft-involving processes. However, the exact mechanism of such regulation is unknown. Although studying rafts in vivo still seems to be rather complicated, liquid-ordered domains are well observed in model systems. In the present study, we used atomic force microscopy (AFM) to examine how lysophospholipids influence the liquid-ordered domains in model ternary membranes. We demonstrated that even a small amount of lysolipids in a membrane significantly impacts domain size depending on the saturation of the lysolipid hydrocarbon tails and the amount of cholesterol. The mixture with the bigger relative fraction of cholesterol was more susceptible to the action of lysolipids. This data helped us to generalize our previous theoretical model of the domain size regulation by lipids with particular molecular shape expanding it to the case of lysolipids and dioleoylglycerol.

Toxic Effects of Penetrating Cations

“…Gangliosides are also known for their ability to alter substantially the ensemble properties of small ordered lipid-protein domains of plasma membranes [12]; such the domains are also called rafts [13]. Similar effects have recently been observed for lysolipids, also having relatively large polar heads and small lipid tails [14]. This result points out that the modification of the raft ensemble properties is not specific to the chemical structure of the particular lipid, e. g, gangliosides, lysolipids.…”

Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content

“…% Chol content, but we did not obtain persistent results, because we were not able to obtain stable supported bilayers with the same protocol. We tried to determine whether APP can act as a line active component like lysolipids and GM1 [ 32 , 33 ], and how it correlates with the amount of cholesterol in a membrane.…”

“…We previously studied lipid rafts as formations with a certain boundary area and line tension (energy of the domain boundary per unit length of its perimeter) in a membrane [ 31 ]. We also investigated how molecules of various molecular geometry influence raft formation [ 32 , 33 ], acting as so-called line active components [ 34 ] and made an analysis of interplay between lipid domains and aging-related diseases [ 35 ]. Here, we used atomic force microscopy to investigate the interaction between the fragment APP 672–726 (corresponding to Aβ 1–55 ) and model membranes containing L o lipid domains with different concentrations of cholesterol for wild-type (WT) and L723P-mutant forms of APP.…”

A Mechanism of Double-Membrane Vesicle Formation from Liquid-Ordered/Liquid-Disordered Phase Separated Spherical Membrane

“…To some extent, the line tension can be regulated by so-called lineactants, i.e., amphiphilic membrane components able to substantially change the line tension being applied in low concentrations (e.g., fractions of mole percent) [ 31 , 32 ]. In particular, monosialoganglioside GM1, lyso-oleoyl-phosphatidyl-choline, and lyso-palmitoyl-phosphatidyl-choline have been recently shown to manifest the line activity in membranes with coexisting L o /L d phases [ 32 , 33 ]. Generally, all membrane components with a non-zero spontaneous curvature are predicted to be line active [ 33 ].…”

“…In particular, monosialoganglioside GM1, lyso-oleoyl-phosphatidyl-choline, and lyso-palmitoyl-phosphatidyl-choline have been recently shown to manifest the line activity in membranes with coexisting L o /L d phases [ 32 , 33 ]. Generally, all membrane components with a non-zero spontaneous curvature are predicted to be line active [ 33 ].…”