Modulation of pathway of insulin fibrillation by a small molecule helix inducer 2,2,2-trifluoroethanol

Victor Banerjee, K. P. Das

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Many proteins form ordered irreversible structural aggregates called amyloid fibrils, which are associated with numerous neurodegenerative diseases. Insulin, a largely α-helical protein associated with type II diabetes, self-assembles to form amyloid fibrils in vitro. Insulin fibrillation goes through a number of intermediate phases that includes a soluble oligomeric phase believed to be the most toxic phase. Small molecules may play a very important role in modulating the fibrillation pathways. It is possible to induce and stabilize helix structures in proteins by a fluorinated alcohol 2,2,2-trifluoro ethanol (TFE). Since fibrillation process of many proteins is associated with conversion of α-helical structures into β-sheet configuration, we thought it would be interesting to study the effect of TFE on the fibrillation of insulin. In absence of TFE, soluble protofibrillar oligomeric intermediates formed directly from the insulin trimer. The protofibrillar aggregates transformed into mature fibrils over time. We demonstrated that although TFE did not prevent the appearance of matured amyloid fibrils, it prevented the appearance of soluble aggregates of insulin. TFE converted the insulin trimer into monomers and fibril formation proceeded from the monomeric state in a cooperative way avoiding the soluble oligomeric phase. At 25% TFE, distinct morphological changes resulting in more discrete fibrils were visible. The effect of the small molecule TFE on the avoidance of the formation soluble oligomeric state during fibrillation may have considerable implications in reducing cellular toxicity.

Original languageEnglish
Pages (from-to)142-150
Number of pages9
JournalColloids and Surfaces B: Biointerfaces
StatePublished - 1 Apr 2012
Externally publishedYes


  • Insulin fibril morphology
  • Insulin fibrillation
  • Kinetics of fibrillation
  • Lag phase
  • Pathway of insulin fibrillation
  • Protofibrillar intermediates
  • Role of TFE

ASJC Scopus subject areas

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


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