Mechanistic Insights into Bioengineered Antibiofilm Enamel Pellicles

Area of Science:

• Biomaterials Science
• Dental Research
• Microbiology

Background:

• Dental caries is a prevalent global chronic disease originating from enamel biofilms.
• Current preventive strategies for enamel caries are limited due to the tissue's nonrenewable nature.
• Customized proteinaceous pellicles have been developed to control bacterial attachment and biofilm formation.

Purpose of the Study:

• To investigate the structure-function relationship of novel hybridized protein conjugates for dental caries prevention.
• To compare the efficacy of hybridized conjugates with individual protein domains in controlling biofilms.
• To elucidate the role of protein folding, structure, and enamel immobilization in antibiofilm activity.

Main Methods:

• Molecular dynamics simulations to assess physicochemical and 3D folding characteristics.
• Circular dichroism to determine adopted secondary structures.
• Multiphoton microscopy to evaluate enamel immobilization capacity.
• Biofilm suppression assays to measure antibiofilm potency.

Main Results:

• Hybridized protein conjugates demonstrated enhanced protein folding and α-helix content compared to individual domains.
• Increased α-helix content correlated with improved enamel immobilization capacity and reduced biofilm formation.
• Anionic N-terminal motifs mediated enhanced immobilization on enamel via a strongly amphipathic helical conformation.

Conclusions:

• Conjugating bioactive proteins/peptides is a promising strategy for engineering robust antibiofilm pellicles.
• The adopted α-helical conformation is crucial for enhancing antibiofilm efficacy and enamel immobilization.
• These findings support the development of novel therapeutics for preventing dental caries, reducing the need for invasive treatments.