Interaction of the α2A domain of integrin with small collagen fragments

Abstract

We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin (α2A), providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular level. The occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy (AFM) techniques. Strong interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study (which contains 42 amino acid residues per strand) by solid phase assays as well as by surface plasmon resonance (SPR) measurements. However, changes in NMR signals during titration and characteristic saturation transfer difference (STD) NMR signals are also detectable when α2A is added to a solution of the 21mer single-stranded collagen fragment. Molecular dynamics (MD) simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments with α2A. It is remarkable that even single-stranded collagen fragments can form various complexes with α2A showing significant differences in the complex stability with identical ligands. The results of MD simulations are in agreement with the signal alterations in our NMR experiments, which are indicative of the formation of weak complexes between single-stranded collagen and α2A in solution. These results provide useful information concerning possible interactions of α2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors.

Collagen Metabolism of Human Osteoarthritic Articular Cartilage as Modulated by Bovine Collagen Hydrolysates

“…Our mass spectrometric analysis as well as NMR experiments enabled us to show for the first time the different characteristic composition and structural organization of the investigated bovine collagen hydrolysates induced by various hydrolysis techniques [14], [15], [37]. Furthermore, we report for the first time about the different biological activities of collagen hydrolysates on human articular chondrocytes, which might be due to different active ingredient(s) of various collagen hydrolysate preparations, as shown by our biophysical analysis.…”

“…Collagen hydrolysates were dissolved in pure water at a concentration of 10 ng/mL, adsorbed onto mica discs (Plano, Germany), incubated for 15 min at room temperature, dried with nitrogen, and imaged under air in tapping mode with OMCL-AC240TS-W2 cantilevers (Atomic force). The data were processed using the MFP-3D interface built on IGOR PRO version 6.02A [14], [15].…”

“…These observations may either contribute to the OA destruction of cartilage or just be normal endogenous metabolic feedback [12], [13]. Another remarkable study was recently published in which a ligand-receptor interaction of small collagen fragments with integrin domains was described, which might serve as a molecular mode of action of collagen hydrolysates [14], [15].…”

Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides

“…It could be demonstrated that different collagen hydrolysates differ in their physico-chemical properties, which could have an impact on the interaction of the peptides with certain integrin receptors (Siebert et al 2010;Stötzel et al 2012). Molecular weight distribution of the collagen peptides and the specific amino acid sequences might be of importance for the efficacy play a major role, whereas the Note: Data are presented as mean VAS Scores ± SEM at baseline (t 0 ) and after 12 weeks (t 12 ).…”

Molecular Basis of the Receptor Interactions of Polysialic Acid (polySia), polySia Mimetics, and Sulfated Polysaccharides

“…However, at concentrations that were higher than 1 mg mL −1 , the sulfated polysaccharides exhibited inhibitory effects on neurite outgrowth. Therefore, the sulfated polysaccharides from mixtures of brown and green algae, with or without bioactive collagen fragments, can also be applied in addition to polySia or polySia mimicking molecules when lesions in neuronal tissues need to be cured …”