Mechanistic Assessment of Functionalized Mesoporous Silica-Mediated Insulin Fibrillation

Authors

Mohsen Akbarian, Shiraz University of Medical Sciences
Lobat Tayebi, Marquette UniversityFollow
Soliman Mohammadi-Samani, Shiraz University of Medical SciencesFollow
Fatemeh Farjadian, Shiraz University of Medical Sciences

Document Type

Article

Publication Date

3-2020

Publisher

American Chemical Society

Source Publication

Journal of Physical Chemistry B

Source ISSN

1520-6106

Abstract

Insulin, which is a small protein hormone consisting of 51 amino acids, rapidly fibrillates under stressogenic conditions. This biotechnological/ medical problematic reaction quickly accelerates in the presence of some particles, while there are several other particles that slow down the kinetic process. To address the unexplored demand of the particles that modulate protein fibrillation, we have synthesized two amino-based particles and a chitosan-coated mesoporous silica particle (MS-NH₂, MS-3NH₂, and MS-chitosan) to investigate insulin fibrillation. While these particles were fairly similar in size, they are differ in their net positive charge and surface hydrophobicity. To monitor the exact role of the hydrophobic interaction between the protein and MS-chitosan during the fibrillation, we have also co- and preincubated insulin with cholesterol and the particles under stressogenic conditions. The results indicate that MS-NH₂ and MS-3NH₂, due to their high positive charges and lack of surface hydrophobicity, repel the positively charged unfolded insulins at pH 2.0. Moreover, MS-chitosan with 25% surface hydrophobicity stacks partially unfolded insulins to its surface and induces some α-helix to β-sheet structural transitions to the protein. Consequently, both amino- and chitosan-based particles slow down the kinetics of the fibrillation. We also showed that cholesterol can structurally participate in insulin fibril architecture as a hydrophobic bridge, and extraction of this molecule from the preformed fibrils may disrupt the fibril structure.

Comments

Accepted version. Journal of Physical Chemistry B, Vol. 124, No. 9 (March 2020): 1637-1652. DOI. © 2020 American Chemical Society. Used with permission.

Recommended Citation

Akbarian, Mohsen; Tayebi, Lobat; Mohammadi-Samani, Soliman; and Farjadian, Fatemeh, "Mechanistic Assessment of Functionalized Mesoporous Silica-Mediated Insulin Fibrillation" (2020). School of Dentistry Faculty Research and Publications. 433.
https://epublications.marquette.edu/dentistry_fac/433