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Physico chemistry of solids, thin films, biotechnologies
Applications for micro & nano- technologies, energy, health ...

> Research > IMBM

Therapeutic protein aggregation at material surfaces

OBJECTIVES

Interactions of proteins with material surfaces are of widespread importance in fields like cellular biology, pharmacology and medicine. Although protein adsorption and aggregation upon contact with material surfaces have been studied since a long time, the role of the material surface itself has often been overlooked.
We have developed sensitive biochemical and biophysical techniques (BCA, AFM, TEM, SPRi, ATR-FTIR, Fluorescence imaging) to study protein adsorption and aggregation kinetics in a quantitative and qualitative way on the material surface. Our model protein is insulin and its material-induced aggregation into amyloid fibers. We explore the effects of different physico-chemical parameters of the material and its environment on protein aggregation. More recently, we are also analysing the effect of dynamic air-liquid interfaces on protein aggregation. Mathematical modeling of protein adsorption and aggregation on material surfaces is another aspect of our research.

Group Members

   Guillaume Lefebvre  (PhD student)
   Dr. Charlotte Vendrely (Visiting researcher)

Highlights

Amyloidogenic peptides accelerate material-induced amyloid aggregation of insulin. Minute amounts of surface-adsorbed peptides are sufficient to trigger insulin aggregation. Stable ß-sheet conformation in the adsorbed state is paramount for these peptides to provide a biomimetic template on which insulin can rapidly bind and change conformation. This then accelerates the stabilization of surface-bound aggregation nuclei, giving rise to amyloid fibers by the addition of incoming insulin molecules from the solution.





Effect of peptides on insulin aggregation kinetics

Selected Publications

Dual Effect of (LK)nL Peptides on the Onset of Insulin Amyloid Fiber
Formation at Hydrophobic Surfaces.
Chouchane K, Vendrely C, Amari M, Moreaux K, Bruckert F, Weidenhaupt M.
J. Phys. Chem. B. 2015.
FEBS Letters. 2013.
Human insulin adsorption kinetics, conformational changes and amyloidal aggregate formation on hydrophobic surfaces.
Nault L, Guo P, Jain B, Bréchet Y, Bruckert F, Weidenhaupt M.
Acta Biomaterialia. 2013.
Surface chemistry at the nanometer scale influences insulin aggregation.
Pandey LM, Le Denmat S, Delabouglise D, Bruckert F, Pattanayek SK, Weidenhaupt M. 
Colloids Surf B Biointerfaces. 2012.
DnaK prevents human insulin amyloid fiber formation on hydrophobic surfaces.
Ballet T, Bruckert F, Mangiagalli P, Bureau C, Boulangé L, Nault L, Perret T, Weidenhaupt M.
Biochemistry. 2012.
Applications of micro- and nanotechnology to study cell adhesion to material surfaces.
Bruckert F, Weidenhaupt M.
J Adhesion Science and Technology. 2010.
 

Date of update April 5, 2018

Univ. Grenoble Alpes