Modeling integrin and plasma-polymerized pyrrole interactions: chemical diversity relevance for cell regeneration

Abstract

Protein-engineered biomaterials represent a powerful approach to increase biofunctional activity like tissue repair and celular proliferation. Among these materials, integrins and the development of their specific interactions with plasma-polymerized pyrrole (PPPy) are promising biomaterial for tissue regeneration. In this paper, we studied the molecular recognition in the active site of three integrins (α5β1, αvβ3 and αIIbβ3) with PPPy using the structure proposed by Kumar et al . PPPy molecule has three sites to incorporate different species, we worked mainly with the functional groups, –NH 2 and –OH groups according to our IR spectroscopic results. We carried out docking studies to find the better conformational couplings and to determine electrostatic (ΔG elec ) and non-electrostatic (ΔG non-elec ) contributions to the binding free energy (ΔG b ) of these complexes we used Adaptive Poisson-Bolztmann program (APBS). Our results indicated that when incorporating -1H-azirine, -NH 2 or –OH group in PPPy structure, interactions with integrins were favorable, as indicated by correspondent ΔG b values. These interactions were mainly triggered by Coulomb interactions, an important term in the electrostatic component. Furthermore, our studies suggest that some residues of integrins α5β1, αvβ3 and αIIbβ3 like aspartates are important for the binding to PPPy structures. Detailed interactions between integrin α5β1 and PPPy structures were revealed by molecular dynamics simulations. We used this particular integrin structure because of its favorable ΔG b as well as its major cellular receptor for the extracellular matrix protein fibronectin. Clustering analysis allowed us to carry out focused docking studies and to determine the time evolution of the ΔG b values. By incorporating -NH 2 into PPPy structure, ΔG b values were very favorable during the course of the dynamics simulations by the establishment of hydrogen bonds with Asn224 and/or Asp227 residues, which are part of the integrin α5β1 pocket. However, for the integrin α5β1-PPPy-1H-azirine complex and the rest of the functional groups, the ΔG b values were less favorable, although PPPy was found at a distance of less than 5 Å from the active site residues. This work is complementary to the previous studies made employing PPPy nanoparticles for a variety of tissue engineering applications, and were done to enlighten the role played by the amino group of the PPPy in its integrin recognition process.

Poly-dopamine, poly-levodopa, and poly-norepinephrine coatings: Comparison of physico-chemical and biological properties with focus on the application for blood-contacting devices

“…Surface functional groups, for example, can directly interact with the integrins on the cell surface, affecting cell adhesion and growth. The incorporation of -NH2 group into plasma-polymerized pyrrole (PPPy) structure, was very favorable to establish hydrogen bonds with Asn224 and/or Asp227 residues, part of the integrin α5β1 pocket [ 45 ]. Wang et al reported that improved growth of ECs by pDA coating was related to the binding of FN to integrin α 5 β 1 [ 46 ].…”

Effect of different exposure times on physicochemical, mechanical and biological properties of PGS scaffolds treated with plasma of iodine-doped polypyrrole

“…From the XPS analysis, an increase in the content of the NH groups on the surface of the PGS scaffolds suggested a possible improvement in cell adhesion, as has been reported to occur in other materials. 16,18,25 However, there is a high probability that these groups are not readily available on the surface of the PPy-I particles to interact with the hDPSCs. Cytotoxicity test results shown in Figure 7(c), revealed that the Live/Dead relationship decreased as the exposure time to the plasma treatment was increased; indicating that the cytotoxicity increases in a directly proportional fashion to the exposure time of the scaffolds to the plasma treatment.…”

“…14 This improvement has been associated with the chemical species that contains N-H bond, which has been proven to stimulate cell growth. 15–17 In this regard, Mejía et al. 18 and Olayo et al., 13 reported that PPy-Mesoparticles, when administered directly into the nerve tissues of rats with spinal cord injury, were successfully integrated into these nerve cells without inducing an acute inflammatory response.…”

Effects of the association of the αvβ8 lower legs on integrin ligand binding

“…In the past few years, many in‐silico techniques have been employed to investigate protein structure prediction and modeling, as well as protein–protein interactions, including molecular docking and molecular dynamics simulations 38–41 . Integrin conformational change and ligand binding have also been studied by computational modeling 42–46 …”