Séminaire LMGP - 24/05/2016 - Karim CHOUCHANE

Karim Chouchane -  PhD student  - LMGP

Abstract

The folding and stability of proteins depend on the physico-chemical conditions of their environment, especially on the pH, temperature, mechanical stresses and on interactions with other macromolecules or with phase interfaces (liquid-material surfaces, air-liquid interface, etc.). Our team focuses on the mechanisms leading to the aggregation of therapeutic proteins on material surfaces (using insulin as model). Previous work at the LMGP have demonstrated that short peptides have the ability to interfere with the kinetics of the surface driven amyloid aggregation. In particular peptides adopting secondary structure in beta-sheet once adsorbed on hydrophobic surfaces were able to reduce the nucleation time of insulin aggregation.

In the present work we have discovered two antagonist effects of peptides presenting alternate sequences: (AB)_n A, these peptides are able to either accelerate or delay insulin amyloid aggregation. We have first shed light on the cooperative behavior of these peptides at the surface of hydrophobic materials resulting in a faster nucleation of insulin aggregates. We then described their opposite effect as strong inhibitors of insulin aggregation in solution and at high concentration.

In addition we studied the localisation of insulin nucleation and developed a technique allowing a localized and patterned growth of insulin aggregates on glass surfaces and explored this method as a mean to obtain quantitative data on protein aggregation at materials surfaces.