Strategically Designed Antifibrotic Gold Nanoparticles to Prevent Collagen Fibril Formation

Abstract

Because uncontrolled accumulation of collagen fibrils has been implicated in a series of pathologies, inhibition of collagen fibril formation has become one of the necessary strategies to target such collagen-linked complications. The presence of hydroxyproline (Hyp) at the Y position in (Gly-X-Y) sequence pattern of collagen is known to facilitate crucial hydrophobic and hydration-linked interactions that promote collagen fibril formation. Here, to target such Hyp-mediated interactions, we have synthesized uniform, thermostable, and hemocompatible Hyp coated gold nanoparticles (AuNPs) and have examined their inhibition effect on the fibril formation of type I collagen. We found that collagen fibril formation is strongly suppressed in the presence of AuNPs and no such suppression effect was observed in the presence of free Hyp and control Gly-coated nanoparticles at similar concentrations. Both isothermal titration calorimetric studies and bioinformatics analysis reveal possible interaction between Hyp and (Gly-Pro-Hyp) stretches of collagen triple-helical model peptides. Further, gold nanoparticles coated with proline (AuNPs) and tryptophan (AuNPs) also suppressed collagen fibril formation, suggesting their ability to interfere with aromatic-proline as well as hydrophobic interactions between collagen molecules. The Hyp molecules, when surface functionalized, are predicted to interfere with the Hyp-mediated forces that drive collagen self-assembly, and such inhibition effect may help in targeting collagen linked pathologies.

The Multifaceted Roles of Proline in Cell Behavior

“…Since L-Pro is a potent and non-toxic chemical chaperone, its intracellular accumulation could be an evolutionarily conserved response aimed at inhibiting the formation of unfolded/misfolded protein aggregates. Indeed, hemocompatible gold nanoparticles coated with L-Pro inhibit both collagen fibril formation (Anand et al, 2017) and insulin aggregation (Prajapati et al, 2021), and could provide a basis for creating antifibrotic and antiamyloid formulations.…”

Controlling the Self-Assembly of Biomolecules into Functional Nanomaterials through Internal Interactions and External Stimulations: A Review

“…Biomolecules can also be conjugated with other nanomaterials, such as graphene or NPs, to form functional nanomaterials via a hydrophobic interaction [67,68,69,70]. For example, Lu and co-workers developed a novel fluorescent approach to monitor peptide–protein interactions based on the assembly of a pyrene-labeled peptide on GO via both π–π and hydrophobic interactions [71].…”

Gelatin grafted poly(D,L‐lactide) as an inhibitor of protein aggregation: An in vitro case study

“…Amyloid fibrils having sizes from microns to nano have been reported by various authors. [4,14,[30][31][32][35][36][37][38][39][40] Figure 1C shows the BSA fibrillation at different time point. After 4 hours, the molecules tried assembling in order and later, they aggregated together and forming the fibrils.…”

“…[11,12] In addition, nanometer-sized materials coated with specific molecules were also found to be capable of inhibiting the fibrillation process of proteins. [4,[13][14][15][16] To the best of our knowledge, very few articles have been reported concerning the synthetic polymers to inhibit the formation of amyloid fibrils. [17][18][19] Poly(lactic acid) (PLA) is a well-known synthetic polymer, widely used in biomedical applications because of its FDA approval for the clinical use.…”