Multivalent 2D- and 3D-nanogels as carbohydrate-lectin binders.

Area of Science:

• Biomaterials Science
• Carbohydrate Chemistry
• Microbiology

Background:

• Targeted bacterial adhesion is a key strategy in developing anti-adhesion therapies.
• Synthetic glycoarchitectures offer a promising approach to modulate bacterial interactions.

Purpose of the Study:

• To synthesize and characterize two distinct mannosylated nanogel architectures (3D spherical and 2D sheet-like).
• To investigate the influence of spatial ligand presentation on multivalent binding interactions with E. coli.
• To evaluate the potential of these glycoarchitectures in anti-adhesion therapy.

Main Methods:

• Nanoprecipitation and removable graphene templating for nanogel synthesis.
• Functionalization with alpha-D-mannose units.
• Characterization using microscale thermophoresis, turbidity measurements, and Cryo-TEM imaging.
• Analysis of E. coli (FimH+) interactions.

Main Results:

• The 3D nanogel exhibited single-site binding behavior with E. coli, confirmed by co-localization with bacterial pili.
• The 2D nanogel displayed distinct dual binding characteristics with varying affinities.
• The high-affinity site of the 2D nanogel showed superior binding compared to the 3D architecture.
• Both nanogels were confirmed to have defined structures, sizes, and surface modifications.

Conclusions:

• Spatial presentation of mannose ligands significantly impacts multivalent binding interactions.
• The distinct binding properties of 3D and 2D nanogels offer opportunities for tailored bacterial targeting.
• These findings contribute to the rational design of advanced glycoarchitectures for combating bacterial adhesion.