Complementary experimental and computational analysis of the effects of non-ionic detergents and phospholipids on insulin amyloid aggregation

Katarina Siposova, Tibor Kozar, Michaela Stupakova, Andrey Musatov

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Amphiphilic compounds, both detergents and lipids, are important tools for in vitro analysis of water-soluble and integral membrane proteins. A key question is whether these two groups of amphiphilic molecules use the same pathway to affect structural and functional integrity of proteins. In the present study, we tested the effect of non-ionic detergent dodecyl maltoside (DDM), two phospholipids, 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC), 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), and the detergent-phospholipid mixtures on insulin amyloidogenesis in vitro. Amyloidogenesis of insulin is significantly affected by DDM in a time-and dose-dependent manner, but only slightly affected by either of phospholipids. Addition of DHPC or DMPC to detergent does not alter the inhibiting pattern, suggesting that DDM preferably binds to insulin. The molecular modeling revealed that DDM and the phospholipids occupy equivalent binding sites. DDM, due to the presence of maltose with several oxygen atoms (hydroxylic, glycosidic and ring) is involved in more hydrogen bonds than DHPC or DMPC. Hydrophobic interactions are important factors to stabilize both, DDM and phospholipids in their binding sites. Our results indicate that certain detergents (applying DDM as an example) and selected phospholipids are not always interchangeable in their use to investigate the effect of amphiphilic compounds on the behavior of amyloid-prone proteins.

Original languageEnglish (US)
Article number111428
JournalColloids and Surfaces B: Biointerfaces
Volume197
DOIs
StatePublished - Jan 2021
Externally publishedYes

Keywords

  • Amyloid aggregation
  • Detergents
  • Hydrogen bonds
  • Hydrophobic interactions
  • Insulin
  • Phospholipids

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

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