Governing the inhibition of reconstituted collagen type I assemblies mediated through non-covalent forces of (±) alpha lipoic acid.

Collagen type I a fibrous protein, is highly biocompatible, biodegradable and exhibits low immunogenicity with its unique feature of undergoing spontaneous self-assembly process. However, the excessive accumulation of collagen may lead to a condition known as fibrosis in a higher form of vertebrates. Plant alkaloids have gained much attention in recent years as the biomedical and therapeutic agents. Therefore, drawing inspiration from the biological and structural tunability of these alkaloids, this work aims to inhibit the self-assembly of type I collagen using (±)-Alpha-lipoic acid (ALA). (±)-ALA is a fatty acid found in broccoli, brussels and meat organ. Reconstituted collagen and its blends with (±)-ALA under physiological conditions were subjected to fibril growth kinetics measurement which exhibited the decrease in the rate of fibrillogenesis (t1/2) 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, it was assayed for the frequency shifts of different functional group via FTIR (ATR) and the morphological changes associated with fibril inhibition was visualizedusing a cryo-scanning electron microscope. Molecular dynamic stimulation of collagen-like peptide with (±)-ALA molecule at different molar ratios proved that (±)-ALA had a strong potential to bind at various sites of collagen-mediated by conventionalsecondary or non-covalent forces. Thus protein-small molecule interaction dominates the forces prevailing between protein-protein binding,which leads to the inhibition of self-assembly process. Such inhibitory effect by a plant alkaloid may unfold newer avenues for development of targeted and sustainable drug delivery systems for fibrotic diseases.