N. Nishad Fathima

Electrostatic Forces Mediated by Choline Dihydrogen Phosphate Stabilize Collagen

Cross-linkers aid in improving biostability of collagen via different mechanisms. Choline dihydrogen phosphate (cDHP), a biocompatible ionic liquid, has been reported as a potential cross-linker for collagen. However, its mechanism is yet unclear. This study explores the effect of cDHP on the physicochemical stability of collagen and nature of its interaction. Dielectric behavior of collagen-cDHP composites signifies that cDHP enhances intermolecular forces. This was demonstrated by an increase in cross-linked groups and high denaturation temperature of collagen-cDHP composites. XRD measurements reveal minor conformational change in helices. Molecular modeling studies illustrate that the force existing between collagen and cDHP is electrostatic in nature. Herein, it is postulated that dihydrogen phosphate anion attaches to cationic functional groups of collagen, resulting in closer vicinity of various side chains of collagen, forming physical and chemical cross-links within collagen, contributing to its structural stability. Our study suggests that dihydrogen phosphate anions can be employed for developing a new class of biocompatible cross-linkers.

Exploiting oleuropein for inhibiting collagen fibril formation

Collagen fibrils accumulate in excessive amounts and impair the normal functioning of the organ; therefore it stimulates the interest for identifying the compounds that could prevent the formation of fibrils. Herein, inhibition of self-assembly of collagen using oleuropein has been studied. The changes in the physico-chemical characteristics of collagen on interaction with increasing concentration of oleuropein has been studied using techniques like viscosity, UV-vis, CD and FT-IR. The inhibitory effect of oleuropein on fibril formation of collagen was proved using SEM. Circular dichroism and FT-IR spectra elucidates the alterations in the secondary structure of collagen suggesting non-covalent interactions between oleuropein and collagen. The decreased rate of collagen fibril formation also confirms the inhibition in the self-assembly of collagen. Hence, our study suggests that inhibition of the self-assembly process using oleuropein may unfold new avenues to treat fibrotic diseases.

Role of Preferential Ions of Ammonium Ionic Liquid in Destabilization of Collagen

Ions play a key role in the destabilization of collagen. This study explores the effect of diethyl methyl ammonium methane sulfonate (AMS), an ionic liquid (IL), on different hierarchical orderings of collagen, namely, at the molecular and fibrillar levels. The rheological behavior and secondary structural changes reveal changes in the hydrogen-bonding environment of collagen, leading to alterations in the triple helical structure of collagen. An increase in the concentration of AMS resulted in swelling of rat-tail tendon fibers, and also, decreased thermal stability signifies that ions are obliged to destabilize collagen at the fibrillar level. Molecular modeling studies confirm that anions are judiciously held responsible for structural deformities in collagen, whereas cations have a tenuous effect. Thus, the preferential role of ions present in an ammonium IL has been elucidated in this study.

Phosphonium based ionic liquids-stabilizing or destabilizing agents for collagen?

Collagen aids in the preparation of biomaterials and its stability is a key factor for these applications. In this study, phosphonium based ionic liquids (PILs) were explored for their stability effects on collagen. The rheology of collagen and UV and fluorescence spectra slackens up with the increasing concentrations. The CD and FT-IR spectra unveil the interaction of the ions in the ionic liquid with the collagen exhibiting denaturation at higher levels. At the inter-fibrillar level, concentration dependent distortion in the banding pattern of RTT collagen fiber was observed due to the chaotropicity of ions. Molecular modeling studies also reveal the ions effect on the stability of collagen and the structural deformation at higher concentrations. Our results show that the ions play an active role on the level of interaction with protein towards the stabilization or destabilization of collagen.

Choline-Based Amino Acid ILs–Collagen Interaction: Enunciating Its Role in Stabilization/Destabilization Phenomena

Given the potential of productive interaction between choline-based amino acid ionic liquids (CAAILs) and collagen, we investigated the role of four CAAILs, viz., choline serinate, threoninate, lysinate, and phenylalaninate, and the changes mediated by them in the structure of collagen at different hierarchical orderings, that is, at molecular and fibrillar levels. The rheological, dielectric behavior and the secondary structural changes signify the alteration in the triple helical structure of collagen at higher concentrations of CAAILs. A marginal swelling and slight decrease in the thermal stability of rat tail tendon collagen fibers were observed for choline serinate and threoninate, albeit distortions in banding patterns were noticed for choline lysinate and phenylalaninate, suggesting chaotropicity of the ions at the fibrillar level. This signifies the changes in the hydrogen-bonding environment of collagen with increasing concentrations of CAAILs, which could be due to competitive hydrogen bonding between the carbonyl group of amino acid ionic liquids and the hydroxyl groups of collagen.

Microenvironmental changes in collagen/polyvinyl alcohol blends in the presence of ionic liquid: A spectroscopic analysis

This study describes the microenvironmental changes due to various non-covalent interactions occurring in collagen/polyvinyl alcohol blends in the presence of ionic liquid, 1-butyl-3-methylimidazolium chloride, using spectroscopic techniques. These non-covalent interactions alter the hydration network of collagen. Electronic spectral analysis of collagen/polyvinyl alcohol/ionic liquid blends exhibited movement of tyrosine amino acid from the hydrophilic to hydrophobic core of collagen. Conformational studies investigating the influence of 1-butyl-3-methylimidazolium chloride on the intramolecular H-bonds revealed increased helicity packing and reorientation of H-bonds. This signifies that 1-butyl-3-methylimidazolium chloride is likely to be involved in reorienting the hydration dynamics of collagen, namely, by altering the existing and promoting formation of new intramolecular H-bonds between collagen and polyvinyl alcohol. Surface morphology of collagen/polyvinyl alcohol/ionic liquid blends revealed porous matrix, indicating 1-butyl-3-methylimidazolium chloride could act as a pore generator. This phenomenon can be employed for developing novel biomaterials with tunable porosity.

Vanillic acid and syringic acid: Exceptionally robust aromatic moieties for inhibiting in vitro self-assembly of type I collagen

Excess collagen fibril accumulation is one of the leading causes for stroke and myocardial infarction, thus inducing interest in identifying and studying the compounds, which inhibits collagen fibril formation. Herein, inhibition of self-assembly of collagen has been studied using syringic acid and vanillic acid. These plant phytochemicals are well known antioxidants and they reduce oxidative stress as well. Inhibitory effect on collagen fibrils using syringic and vanillic acid has been studied using varying biophysical techniques. Circular Dichroism and FT-IR studies clearly showed the changes in secondary structure of collagen with the increasing concentration of vanillic acid and syringic acid. DLS measurements showed an acute aggregation upon treatment with these compounds and an inhibitory effect was also visualized using morphological studies. In addition, the decreased rate in the formation of collagen fibrils proves that these compounds are efficient to inhibit collagen fibril formation. This opens a new arena for the development of novel targeted delivery systems for diseases related to collagen accumulation.