Modulatory Effect of Glycated Collagen on Oral Streptococcal Nanoadhesion

Abstract

Biofilm-mediated oral diseases such as dental caries and periodontal disease remain highly prevalent in populations worldwide. Biofilm formation initiates with the attachment of primary colonizers onto surfaces, and in the context of caries, the adhesion of oral streptococci to dentinal collagen is crucial for biofilm progression. It is known that dentinal collagen suffers from glucose-associated crosslinking as a function of aging or disease; however, the effect of collagen crosslinking on the early adhesion and subsequent biofilm formation of relevant oral streptococci remains unknown. Therefore, the aim of this work was to determine the impact of collagen glycation on the initial adhesion of primary colonizers such as Streptococcus mutans UA159 and Streptococcus sanguinis SK 36, as well as its effect on the early stages of streptococcal biofilm formation in vitro. Type I collagen matrices were crosslinked with either glucose or methylglyoxal. Atomic force microscopy nanocharacterization revealed morphologic and mechanical changes within the collagen matrix as a function of crosslinking, such as a significantly increased elastic modulus in crosslinked fibrils. Increased nanoadhesion forces were observed for S. mutans on crosslinked collagen surfaces as compared with the control, and retraction curves obtained for both streptococcal strains demonstrated nanoscale unbinding behavior consistent with bacterial adhesin-substrate coupling. Overall, glucose-crosslinked substrates specifically promoted the initial adhesion, biofilm formation, and insoluble extracellular polysaccharide production of S. mutans, while methylglyoxal treatment reduced biofilm formation for both strains. Changes in the adhesion behavior and biofilm formation of oral streptococci as a function of collagen glycation could help explain the biofilm dysbiosis seen in older people and patients with diabetes. Further studies are necessary to determine the influence of collagen crosslinking on the balance between acidogenic and nonacidogenic streptococci to aid in the development of novel preventive and therapeutic treatment against dental caries in these patients.

Nanomechanical and molecular characterization of aging in dentinal collagen

“…In the >50yo group however, there is a significant increase in PT collagen elasticity to a median of 9.25 (95% CI[8.73-9.73]) GPa ( Figure 2C ; p<0.0001, Kruskal-Wallis test). AGE accumulation has been shown to increase the YM of collagen in both in-vitro and tissue experiments (Verzijl et al 2002; Depalle et al 2015; Panwar et al 2015; Schuh et al 2021), suggesting that the increase in elasticity observed in PT collagen is mediated by the accumulation of MGO adducts and other potential AGEs and crosslinks (Lederer and Bühler 1999). As PT dentin is located immediately adjacent to the dentinal tubules, the presence of glucose and MGO in the pulp-derived perfusing fluid could explain collagen modification and the formation of AGEs over time (Miura et al 2014).…”

“…A different pattern is observed in >50yo patients, where there is less association amongst the studied variables, and separation is explained by a combination of the PC1 and PC2 components ( Figure 4E ). These distinctive nanomechanical and molecular profiles observed in >50yo samples strengthen the importance of further understanding how the process of aging impacts the mechanical properties of dentinal collagen Additionally, future work is needed to understand the potential impact of these aging-associated collagen changes on restorative dentistry approaches such as adhesive bonding to dentin and hybrid layer formation (Breschi et al 2018), on bacterial adhesion and degradation during dentinal and root caries progression (Schuh et al 2021; Álvarez et al 2021), and on root caries restoration in the elderly.…”

“…A total of 100 force-distance curves were obtained per image (50 PT + 50 IT), for a total of 300 curves across the three areas of each sample. From the resulting force-distance curves, dentinal collagen Young's moduli (YM) were calculated utilizing the Derjaguin, Muller, and Toporov (DMT) model in the proprietary Asylum Research AFM software (v. 16.10.211) (Schuh et al 2021).…”

A Review of the Effects of Collagen Treatment in Clinical Studies

“…However, it remains unknown how collagen crosslinking affects the early adhesion of related oral streptococci. Schuh et al studied the effect of glycated collagen on oral streptococcal nanoadhesion to help develop a new preventive and therapeutic treatment against dental caries [99].…”

Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis

“…One other protein, which is also glycated in vivo, is collagen, the most abundant, long-life structural protein in the human body [ 29 , 32 , 33 ]. This protein has a hierarchical arrangement originating from the polymerization of collagen molecules into fibrils and, owing to its abundant lysine residues, is also subjected to intermolecular crosslinking from glycation [ 29 , 32 , 33 , 34 , 35 , 36 ].…”