Self-Organisation, Thermotropic and Lyotropic Properties of Glycolipids Related to their Biological Implications

Abstract

Glycolipids are amphiphilic molecules which bear an oligo- or polysaccharide as hydrophilic head group and hydrocarbon chains in varying numbers and lengths as hydrophobic part. They play an important role in life science as well as in material science. Their biological and physiological functions are quite diverse, ranging from mediators of cell-cell recognition processes, constituents of membrane domains or as membrane-forming units. Glycolipids form an exceptional class of liquid-crystal mesophases due to the fact that their self-organisation obeys more complex rules as compared to classical monophilic liquid-crystals. Like other amphiphiles, the supra-molecular structures formed by glycolipids are driven by their chemical structure; however, the details of this process are still hardly understood. Based on the synthesis of specific glycolipids with a clearly defined chemical structure, e.g., type and length of the sugar head group, acyl chain linkage, substitution pattern, hydrocarbon chain lengths and saturation, combined with a profound physico-chemical characterisation of the formed mesophases, the principles of the organisation in different aggregate structures of the glycolipids can be obtained. The importance of the observed and formed phases and their properties are discussed with respect to their biological and physiological relevance. The presented data describe briefly the strategies used for the synthesis of the used glycolipids. The main focus, however, lies on the thermotropic as well as lyotropic characterisation of the self-organised structures and formed phases based on physico-chemical and biophysical methods linked to their potential biological implications and relevance.

Polymorphic Regulation of Outer Membrane Lipid A Composition

“…As expected, the hepta-acylated lipid A has a larger cross-sectional molecular shape than its hexa-acylated counterpart, and it takes on a perceptible increase in conical shape. In accordance with the predictions of Brandenburg and coworkers (8, 9), we expect palmitoylated lipid A to stimulate an increase in the inflammatory response. Indeed, when C 16 is esterified to the distal glucosamine unit in Pseudomonas aeruginosa lipid A, an increase in the inflammatory response is observed, and this is thought to result from a superior ability of this modified lipid A to bind within the MD-2 receptor of the TLR4–MD-2 complex (14).…”

“…1B). Brandenburg and coworkers have shown that lipid A molecules that adopt cylindrical shapes tend to be inactive as endotoxins but that those that are the most endotoxic tend to be more conical and tilted in shape (8, 9). The crystal structures of the TLR4–MD-2 complexes with various lipid A analogues reveal the molecular bases for how lipid A structure influences the innate immune response (10, 11), but lipid A evolved to function in the outer membranes of Gram-negative bacteria long before the evolution of multicellular eukaryotes.…”

TRP Channels as Sensors of Chemically-Induced Changes in Cell Membrane Mechanical Properties

“…Lipid bilayers are composed of two opposing leaflets made of multiple, asymmetrically distributed lipids species, belonging to the main three classes, including glycerophospholipids, sphingolipids and sterols [66,67,68]. Amphipathic lipids, consisting of polar, hydrophilic head groups and apolar, hydrophobic chains, tend to aggregate in the lipid-water systems into specific phases such as micelles, lamellar, cubic or inverse hexagonal phases [69,70]. This supramolecular phase organization is driven by the shape and concentration of the amphipathic molecule as well as the system’s temperature.…”

Recent Advances in the Chemistry of Glycoconjugate Amphiphiles

“…For Cell-Tz-C 16 and Lact-Tz-C 16 the liquid crystalline phases (mesophases) appeared above 150 °C, and Smectic A phase (molecules are directionally ordered into layers) for the latter compounds was evidenced by X-ray diffraction. Of course, dealing with LC properties of GLs is beyond the scope of this account and further reading and examples can be found elsewhere [ 95 , 96 , 97 ]. Note, however, that thermotropic LC phases were much less studied than LC structures formed in water, and other biomolecules can form such materials [ 98 ].…”