Governing the Inhibition of Reconstituted Collagen Type I Assemblies Mediated Through Noncovalent Forces of (±)-α...

Type I collagen is a fibrous protein, which is highly biocompatible and biodegradable and exhibits low immunogenicity with its unique feature of undergoing a spontaneous self-assembly process. However, the excessive accumulation of collagen may lead to a condition known as fibrosis in vertebrates. Recently, saturated fatty acids have gained much attention as biomedical and therapeutic agents. Therefore, drawing inspiration from the biological and structural tunability of these fatty acids, this work aims to inhibit the self-assembly of type I collagen using (±)-α-lipoic acid (ALA). Reconstituted collagen and its blends with (±)-ALA under physiological conditions were subjected to fibril growth kinetics measurements, which exhibited the decrease in the rate of fibrillogenesis ( t_1/2) with an increase in the concentration of ALA. Variations in the viscoelasticity of collagen and ALA blend with respect to rate and frequency showed significant changes. Further, the frequency shifts of different functional groups via FT-IR (ATR) and the morphological changes associated with fibril inhibition were visualized using a cryoscanning electron microscope. Molecular dynamics simulation of the collagen-like peptide with the (±)-ALA molecule at different molar ratios proved that (±)-ALA had a strong potential to bind at various sites of collagen mediated by conventional secondary or noncovalent forces. Thus, the protein-small molecule interaction dominates the forces prevailing between protein-protein binding, leading to the inhibition of the self-assembly process. Such inhibitory effects by a fatty acid may unfold newer avenues for development of targeted and sustainable drug delivery systems for fibrotic diseases.