Title
Strategically Designed Antifibrotic Gold Nanoparticles to Prevent Collagen Fibril Formation
Author
Bibin Ganadhason Anand, Kriti Dubey, Dolat Singh Shekhawat, Kailash Prasad Prajapati, Karunakar Kar
Year
2017
Journal
Langmuir
Abstract
Because uncontrolled accumulation of collagen fibrils has been implicated in a series of pathologies, inhibition of collagen fibril formation has become one of the necessary strategies to target such collagen-linked complications. The presence of hydroxyproline (Hyp) at the Y position in (Gly-X-Y)n sequence pattern of collagen is known to facilitate crucial hydrophobic and hydration-linked interactions that promote collagen fibril formation. Here, to target such Hyp-mediated interactions, we have synthesized uniform, thermostable, and hemocompatible Hypcoated gold nanoparticles (AuNPsHYP) and have examined their inhibition effect on the fibril formation of type I collagen. We found that collagen fibril formation is strongly suppressed in the presence of AuNPsHYP and no such suppression effect was observed in the presence of free Hypand control Gly-coated nanoparticles at similar concentrations. Both isothermal titration calorimetric studies and bioinformatics analysis reveal possible interaction between Hyp and (Gly-Pro-Hyp) stretches of collagen triple-helical model peptides. Further, gold nanoparticles coated with proline (AuNPsPRO) and tryptophan (AuNPsTRP) also suppressed collagen fibril formation, suggesting their ability to interfere with aromatic-proline as well as hydrophobic interactions between collagen molecules. The Hyp molecules, when surface functionalized, are predicted to interfere with the Hyp-mediated forces that drive collagen self-assembly, and such inhibition effect may help in targeting collagen linked pathologies.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Nanostructures, Biochemistry, Materials