Mannose Surfaces Exhibit Self-Latching, Water Structuring, and Resilience to Chaotropes: Implications for Pathogen Virulence

Abstract

Several viral and fungal pathogens, including HIV, SARS, Dengue, Ebola, and Cryptococcus neoformans, display a preponderance of mannose residues on their surface, particularly during the infection cycle or in harsh environments. The innate immune system, on the other hand, abounds in mannose receptors which recognize mannose residues on pathogens and trigger their phagocytosis. We pose the question if there is an advantage for pathogens to display mannose on their surface, despite these residues being recognized by the immune system. The surface properties and interactions of opposing monolayers of mannobiose (disaccharide of mannose) were probed using atomic force spectroscopy. Unlike its diastereoisomer lactose, mannobiose molecules exhibited lateral packing interactions that manifest on the surface scale as a self-recognizing latch. A break-in force is required for opposing surfaces to penetrate and a breakout (or self-adhesion force) of similar magnitude is required for penetrated surfaces to separate. A hierarchy of self-adhesion forces was distinguished as occurring at the single residue (∼25 pN), cluster (∼250 pN), monolayer (∼1.1 nN), and supramonolayer level. The break-in force and break-out force appear resilient to the presence of simple chaotropes that attenuate a layer of structured water around the mannose surface. The layer of structured water otherwise extends to distances several times longer than a mannobiose residue, indicating a long-range propagation of the hydrogen bonding imposed by the residues. The span of the structured water increases with the velocity of an approaching surface, similar to shear thickening, but fissures at higher approach velocities. Our studies suggest that mannose residues could guide interpathogen interactions, such as in biofilms, and serve as a moated fortress for pathogens to hide behind to resist detection and harsh environments.

Mannobiose‐Grafting Shifts PEI Charge and Biphasic Dependence on pH

“…Mannobiose residues, like other glycans, are known to engage in extensive cooperative hydrogen bonds with a polarizable solvent . In atomic force spectroscopy, the resulting structured water over mannobiose monolayers resists the approach of a probe as far as 35 nm away . We investigate if the reduction in PEI protonability by mannobiose is related to the latter's hydrogen‐bonding properties.…”

“…APCs like dendritic cells and Langerhan cells have surface receptors for mannose. We also recently reported extensive water‐structuring and self‐adhesion properties arising from monolayers of mannobiose bristles in force spectroscopy experiments …”

“…[52,53] In atomic force spectroscopy, the resulting structured water over mannobiose monolayers resists the approach of a probe as far as 35 nm away. [34] We investigate if the reduction in PEI protonability by mannobiose is related to the latter's hydrogen-bonding properties. Salt ions, being charged and diffusive, interfere with the ordering of the water molecules [54] ; the observed salt-induced increase in PEIm protonability can be related to the associated decrease in cooperative hydrogen bonding and water-structuring.…”

“…We also recently reported extensive water-structuring and self-adhesion properties arising from monolayers of mannobiose bristles in force spectroscopy experiments. [34] This paper is organized in two parts. The first part determines how mannobiosylation alters the pH dependence of PEI charge, zeta potential, and hydrodynamic radius.…”

Glycomics and Proteomics Approaches to Investigate Early Adenovirus–Host Cell Interactions

“…Examples of lectins are Ctype lectins such as DC-SIGN, which is expressed on dendritic cells and contributes to cell-cell adhesion [55]. DC-SIGN and other C-type lectins bind to mannosecontaining glycans that commonly decorate viral spikes [56]. While several viruses have been reported to interact with C-type lectins, a clear role in cell entry has mainly been demonstrated for phleboviruses, dengue virus, and West Nile virus [57].…”