Abstract
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.
Highlights
Glycosaminoglycans (GAGs) are essential components of the extracellular matrices (ECMs) that contribute to the stability, development, and communication of natural cells within all kinds of tissues (Bosman and Stamenkovic 2003; Saridaki et al 2012)
In order to determine the effect of DS40 on model cellular membrane, in the first step of our investigations, we have examined its influence separately on two major membrane lipids: cholesterol and DPPC, and subsequently on cholesterol/DPPC mixed monolayers as a simplified biomembrane model
The behavior of the above membrane lipids and their mixtures have already been studied in detail (CadenaNava et al 2006; Sabatini et al 2008; Miñones et al 2009), we present the π/A isotherms and Brewster Angle Microscopy (BAM) images recorded on water subphase for the purpose of comparison with the results obtained for DS40 and/or Ca2+-containing subphases
Summary
Glycosaminoglycans (GAGs) are essential components of the extracellular matrices (ECMs) that contribute to the stability, development, and communication of natural cells within all kinds of tissues (Bosman and Stamenkovic 2003; Saridaki et al 2012). GAGs belong to the group of polysaccharides composed of long unbranched carbohydrate chains with repeating disaccharide units of an amino sugar (either N-acetylglucosamine or N-acetylgalactosamine) along with an uronic acid sugar (either glucuronic acid or iduronic acid) or galactose Molecular structures of GAGs that naturally occur in living cells are rather uncomplicated, these polysaccharides can be subjected to further transformations, including enzymatic sulfonation of hydroxyl groups in carbohydrate moieties. A number of GAGs derivatives can be formed; both sulfated (including heparin and heparan sulfate, keratan sulfate, chondroitin sulfate, and dermatan sulfate) and non-sulfated (e.g., hyaluronic acid) (Lindahl and Li 2009; Papy-Garcia et al 2011)
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