The Effect of Dextran Sulfate-as Model Glycosaminoglycan Analogue-on Membrane Lipids: DPPC, Cholesterol, and DPPC-Cholesterol Mixture. The Monolayer Study.

Glycosaminoglycans (GAGs) are essential components of the extracellular matrices (ECMs) located on the outer surface of cellular membranes. They belong to the group of polysaccharides involved in diverse biological processes acting on the surface and across natural lipid membranes. Recently, particular attention has been focused on possible role of GAGs in the amyloid deposits. The amyloid formation is related to a disorder in protein folding, causing that soluble-in normal conditions-peptides become deposited extracellularly as insoluble fibrils, impairing tissue structure and its function. One of the hypothesis holds that GAGs may inhibit amyloid formation by interacting with the lipid membrane by blocking the accumulation of protein aggregates on the membrane surface. Although the biophysical properties of GAGs are described rather well, little is known about the nature of association between these polysaccharides and components of natural cell membranes. Therefore, a study of GAGs influence on membrane lipids is of particular importance. The aim of the present work is to get insight into the effect of hydrophilic dextran sulfate (DS)-that can be considered as GAG analogue-on membrane lipids organization. This study was based on examining interactions between DS sodium salt of molecular weight equal to about 40 kDa (DS40), dissolved in water subphase, and a model membrane, mimicked as Langmuir monolayer, formed by representative natural membrane lipids: cholesterol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as well as their mixtures. Due to the fact that calcium ions in excess may accumulate in the lipid membrane, attracting high molecular weight molecules to their surface, the influence of calcium ions present in the subphase on the DS40 activity has also been examined. It has been found that negatively charged DS, forming a sublayer underneath the monolayer, barely interacts with membrane lipids; however, in the presence of calcium ions the electrostatic interactions between DS40 and lipid membrane are significantly enhanced, leading to the formation of network-like crystalline structures at the surface of model membrane, which can prevent incorporation and interaction with other extracellular molecules, e.g., proteins.