Carbohydrate‐Carbohydrate Interactions

Abstract

Cell recognition and adhesion are important events in the formation and maintenance of functional tissues. These processes must be selective and flexible in order to guarantee proper development as in embryogenesis, during the development of the nervous system, for continuous activity of the lymphoid system, but can also be misused by parasitic intruders or aberrant cells like tumor cells. How are glycans involved in these recognition and adhesion phenomena so important for all living organisms?Carbohydrates are the most ubiquitous and prominently exposed molecules on the surface of living cells. The combination of a few building blocks in a seemingly countless array of structures is a principle characteristic of carbohydrate chains that distinguishes carbohydrate sequences from all other biomolecules whether nucleic acids or peptides. Such, these chains offer simultaneously flexible, ordered and easily modulatable motives for cellular interactions. The specific arrangement of individual carbohydrate sequences on surfaces and within matrices creates yet another dimension of diversity: Well defined structures or patches of carbohydrate motives can be created within linear stretches of glycans and glycosaminoglycans (GAG), attached to core protein backbones or located on freely movable lipid anchors for interaction with other molecules [ 1, 21. Glycans are therefore predestined to serve as crucial molecules for recognition and attachment at the moment of cell encounter,Carbohydrates have been recognized as interaction sites in many different instances. Many of these processes are mediated by lectin-or lectin-like molecules that recognise specific carbohydrate motifs. Lymphocyte homing is a multistep process with increasing interaction strengths. A first rolling stage of circulating lymphocytes is dependent on recognition of glycan ligands by protein receptors, the selectins, on the endothelium as well as on the lymphocytes [2, 31. Neuronal development depends on reversible cell extensions and connections followed by disruption which requires the proper interaction with cells, extracellular matrix and solu- Carbohydrates in Chemistry

Proteoglycan Mechanics Studied by Single-molecule Force Spectroscopy of Allotypic Cell Adhesion Glycans

“…The sulfated disaccharide self-associated in the presence of Ca 2ϩ , but the interaction was completely eradicated on substitution of Ca 2ϩ ions by either Mg 2ϩ or Mn 2ϩ ions. This is consistent with a rapid multiple low affinity event where Ca 2ϩ provides not only electrostatic forces but contributes via coordinative forces to glycan superstructures (6,46). In this scenario, simple charge effects may lead to nonspecific interactions in low calcium concentrations that might be overcome when more calcium is present, allowing the organization of sugar moieties and enhancing the adhesion between specific carbohydrate groups.…”

“…However, carbohydrate structures have immense structural diversity (2), a ubiquitous distribution in vertebrate and invertebrate tissues (3), and are associated with the cell surface (4,5), as required of cell recognition molecules. Carbohydrate-carbohydrate interactions are characterized by relatively weak forces that, when multimerized, can be easily potentiated by orders of magnitude, representing a highly versatile form of cell adhesion given the extraordinary plasticity of their structures (6). Among the few known examples of carbohydrate self-recognition proposed to be specific in biological processes are the multivalent binding of Lewis x epitopes involved in the first steps of embryogenesis (7,8), glycolipid-glycolipid interactions controlling cell adhesion, spreading, and motility (9 -11), and self-interactions of the glycan portion of sponge proteoglycans leading to species-specific cell adhesion (12,13).…”

Carbohydrate-Carbohydrate Interactions Mediated by Sulfate Esters and Calcium Provide the Cell Adhesion Required for the Emergence of Early Metazoans

“…Similar characteristics were observed for the calcium-free self-interactions of g200 from M. prolifera (5). These calciumand/or sulfate-free interactions likely operate through hydrogen bonds between hydroxyl groups on the polysaccharides, whereas the excess of Na ϩ ions in seawater neutralizes the repulsive forces expected from the highly anionic sulfate and carboxyl groups (10). The ability of calcium ions to provide adequate molecular landscapes for such interactions (5) was also observed because the binding forces measured for the desulfated derivative in the presence of calcium were slightly stronger than in experiments conducted in the absence of calcium.…”

“…17), the homophilic and calcium-dependent self-interactions between sulfated polysaccharides components of AFs are the primary forces driving cell-cell adhesion in sponges. These interaction forces have been attributed to hydrogen bonds between the hydroxyl groups of sugar moieties of polysaccharides (10). In this model calcium ions are responsible only for the approach and organization of the sugar moieties and provide adequate surfaces for further interactions (5).…”

“…Carbohydrate selfadhesion is maintained by relatively weak forces that can increase in orders of magnitude upon the multimerization of individual epitopes into polysaccharides (10). Some examples of specific carbohydrate self-interactions include the multivalent binding of Lewis x epitopes involved in the first steps of embryogenesis (11), glycolipid-glycolipid interactions controlling cell adhesion, spreading, and motility (12), and self-interactions of sulfated polysaccharides leading to species-specific cell adhesion in sponges (13).…”