posted on 2017-10-26, 00:00authored byBibin
Ganadhason Anand, Kriti Dubey, Dolat Singh Shekhawat, Kailash Prasad Prajapati, Karunakar Kar
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 Hyp coated 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 Hyp and 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.