Abstract
Glycosaminoglycans (GAGs) are natural, linear and negatively charged heteropolysaccharides which are incident in every mammalian tissue. They consist of repeating disaccharide units, which are composed of either sulfated or non-sulfated monosaccharides. Depending on tissue types, GAGs exhibit structural heterogeneity such as the position and degree of sulfation or within their disaccharide units composition being heparin, heparan sulfate, chondroitine sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. They are covalently linked to a core protein (proteoglycans) or as free chains (hyaluronan). GAGs affect cell properties and functions either by direct interaction with cell receptors or by sequestration of growth factors. These evidences of divert biological roles of GAGs make their characterization at cell and tissue levels of importance. Thus, non-invasive techniques are interesting to investigate, to qualitatively and quantitatively characterize GAGs in vitro in order to use them as diagnostic biomarkers and/or as therapeutic targets in several human diseases including cancer. Infrared and Raman microspectroscopies and imaging are sensitive enough to differentiate and classify GAG types and subtypes in spite of their close molecular structures. Spectroscopic markers characteristic of reference GAG molecules were identified. Beyond these investigations of the standard GAG spectral signature, infrared and Raman spectral signatures of GAG were searched in complex biological systems like cells. The aim of the present review is to describe the implementation of these complementary vibrational spectroscopy techniques, and to discuss their potentials, advantages and disadvantages for GAG analysis. In addition, this review presents new data as we show for the first time GAG infrared and Raman spectral signatures from conditioned media and live cells, respectively.
Highlights
Pathophysiological aspects of glycosaminoglycansGlycosaminoglycans (GAGs) and proteoglycans (PGs) are major constituents of the extracellular matrix (ECM)
The aim of the present review is to describe the implementation of these complementary vibrational spectroscopy techniques, and to discuss their potentials, advantages and disadvantages for GAG analysis
The chemical analysis of such preparations is a tedious task involving enzymatic depolymerisation of GAG chains with specific bacterial enzymes followed by disaccharide analysis with Gel Permeation Chromatography (GPC) [27], High-Performance-Liquid Chromatography (HPLC), Ultra-Performance Liquid Chromatography (UPLC) [28], Nuclear Magnetic Resonance (NMR) spectroscopy, Mass Spectrometry (MS) [29], Capillary Electrophoresis (CE) [30] and Fluorophore Assisted Carbohydrate Electrophoresis (FACE) [31, 32]
Summary
Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major constituents of the extracellular matrix (ECM). PGs are present at the cell surface, in the ECM, in intracellular granules and in basement membranes [1]. GAGs are unbranched and negatively charged heteropolysaccharides composed of repeating disaccharide units of alternating uronic acids and N-acetylated hexosamine [2]. Most of GAGs are covalently attached to core proteins to form PGs [3, 4]. HA is a non-sulfated GAG devoid of a covalently bound core protein. They modulate cell growth-factor activation, regulate collagen fibrillogenesis, affect tumor cell growth and invasion, and influence corneal transparency. The first known biological function of GAGs is the clinical anticoagulant role of HEP. Numerous genetic studies on GAG biosynthetic enzymes revealed direct evidences of involvement of GAGs in cell growth including transforming growth factor (TGF), and fibroblast growth factor (FGF) signalling pathways [11]
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