Mannose moieties exhibit self‐adhesive interactions

Carbohydrate‐Carbohydrate interactions (CCIs) are self‐adhesive interactions, generally observed among proteoglycans and glycolipids expressed on the cell surfaces. Many biological processes such as embryogenesis, fertilization and metastasis are driven by CCIs. Mannoses are biologically‐significant carbohydrate moieties, that are extensively present on the surfaces of fungi and viruses, and known to mediate host‐pathogen interactions. We studied the adhesive interactions between mannobiose (disaccharides of mannose sugars)‐mannobiose molecules using atomic force spectroscopy (AFS). Bifunctional linkers were synthesized with thiol functional groups on one end and aryl‐azide functional group on the other. The linkers were self‐assembled on gold substrates (gold coated AFM sample disks and gold coated AFM probes) via the thiol end, and mannobiose was photochemically linked to the free aryl‐azide end of the surface‐anchored linkers. The mannobiose attachment on the substrates was verified via its selective binding to the lectin, concanavalin‐A. Mannobiose‐mannobiose molecules exhibited strong adhesive forces when probed with AFS in an aqueous medium. The force‐distance curves exhibited peak adhesive forces that subsequently ruptured in ‘step’ like patterns, indicating that the adhesive forces were due to well‐defined molecular interactions. The peak adhesive forces between mannobiose‐mannobiose molecules ranged from 0.3 to 5.7 nN. The final ‘step’ or rupture forces ranged from 0.1 to 1nN, with forces clustering at regular intervals which were multiples of 25 +/− 3pN. The latter suggests the likely magnitude of the single mannose‐mannose unbinding force to be 25 +/− 3pN. Lactose, a diastereoisomer of mannobiose, did not show self‐adhesive interactions. Free mannobiose reduced the mannobiose‐mannobiose adhesive forces in a concentration‐dependent manner; whereas free lactose was less effective in reducing the forces. Also, the mannobiosylated surface displayed ‘water structuring’ effects that extended tens of nanometers beyond the surface, and which were disrupted by increasing the salt concentration. This is the first study to report self‐adhesive function between mannobiosylated surfaces. The majority of fungi and virulent viruses such as HIV, Ebola, and Marburg have mannose patches on their surfaces, and this fundamental study might shed light on the biophysical role of these pathogen surfaces. The water‐structuring ability of clustered mannose molecules may manifest as a dense water shell around pathogens, to keep them hydrated and protected from host immune molecules. Support or Funding Information This work is supported by National Science Foundation under grant no. 1407891 awarded to Dr. Preethi Chandran and by a mini‐grant awarded to Dr. Preethi Chandran under NSF grant no. 1208880 (PI: Dr. Sonya Smith)