The degree of unsaturation of fatty acids in phosphatidylserine alters the rate of insulin aggregation and the structure and toxicity of amyloid aggregates.

Abstract

Phosphatidylserine (PS) in the plasma membrane plays an important role in cell signaling and apoptosis. Cell degeneration is also linked to numerous amyloid diseases, pathologies that are associated with aggregation of misfolded proteins. In this work, we examine the effect of both saturated PS (DMPS) and unsaturated PS (DOPS and POPS) on the aggregation properties of insulin, as well as the structure and toxicity of insulin aggregates formed in the presence of these phospholipids. We found that the degree of unsaturation of fatty acids in PS alters the rate of insulin aggregation. We also found that toxicity of insulin-DMPS aggregates is significantly lower than the toxicity of DOPS- and POPS-insulin fibrils, whereas all these lipid-containing aggregates exert lower cell toxicity than insulin fibrils grown in a lipid-free environment.