PMID- 23707907 OWN - NLM STAT- MEDLINE DCOM- 20130827 LR - 20171116 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1828 IP - 9 DP - 2013 Sep TI - Evaluation of membrane models and their composition for islet amyloid polypeptide-membrane aggregation. PG - 2091-8 LID - S0005-2736(13)00160-0 [pii] LID - 10.1016/j.bbamem.2013.05.014 [doi] AB - Human islet amyloid polypeptide (IAPP) forms amyloid fibrils in the pancreatic islets of patients suffering from type 2 diabetes mellitus (T2DM). The formation of IAPP fibrils has been shown to cause membrane damage which most likely is responsible for the death of pancreatic islet beta-cells during the pathogenesis of T2DM. Several studies have demonstrated a clear interaction between IAPP and lipid membranes. However the effect of different lipid compositions and of various membrane mimetics (including micelles, bicelles, SUV and LUV) on fibril formation kinetics and fibril morphology has not yet systematically been analysed. Here we report that the interaction of IAPP with various membrane models promoted different processes of fibril formation. Our data reveal that in SDS and DPC micelles, IAPP adopts a stable alpha-helical structure for several days, suggesting that the micelle models may stabilize monomeric or small oligomeric species of IAPP. In contrast, zwitterionic DMPC/DHPC bicelles and DOPC SUV accelerate the fibril formation compared to zwitterionic DOPC LUV, indicating that the size of the membrane model and its curvature influence the fibrillation process. Negatively charged membranes decrease the lag-time of the fibril formation kinetics while phosphatidylethanolamine and cholesterol have an opposite effect, probably due to the modulation of the physical properties of the membrane and/or due to direct interactions with IAPP within the membrane core. Finally, our results show that the modulation of lipid composition influences not only the growth of fibrils at the membrane surface but also the interactions of beta-sheet oligomers with membranes. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Caillon, Lucie AU - Caillon L AD - UPMC Univ Paris 06, UMR 7203 CNRS-UPMC-ENS, Laboratoire des Biomolecules, 4 place Jussieu, 75005 Paris, France. FAU - Lequin, Olivier AU - Lequin O FAU - Khemtemourian, Lucie AU - Khemtemourian L LA - eng PT - Journal Article DEP - 20130523 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (1,2-dihexadecyl-sn-glycero-3-phosphocholine) RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Lipid Bilayers) RN - 0 (Micelles) RN - 0 (Phosphatidylcholines) RN - 0 (Phosphatidylethanolamines) RN - 0 (Phospholipid Ethers) RN - 0 (Unilamellar Liposomes) RN - 97C5T2UQ7J (Cholesterol) RN - EDS2L3ODLV (1,2-oleoylphosphatidylcholine) RN - U86ZGC74V5 (Dimyristoylphosphatidylcholine) SB - IM MH - Cholesterol/*chemistry MH - Dimyristoylphosphatidylcholine/*chemistry MH - Humans MH - Islet Amyloid Polypeptide/*chemistry/ultrastructure MH - Lipid Bilayers/*chemistry MH - Micelles MH - Microscopy, Electron MH - Models, Biological MH - Phosphatidylcholines/*chemistry MH - Phosphatidylethanolamines/*chemistry MH - Phospholipid Ethers/*chemistry MH - Protein Structure, Secondary MH - Static Electricity MH - Unilamellar Liposomes/chemistry OTO - NOTNLM OT - 1,1,1,3,3,3-hexafluoro-2-propanol OT - 1,2-dihexanoyl-sn-glycero-3-phosphocholine OT - 1,2-dimyristoyl-sn-glycero-3-phosphocholine OT - 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) OT - 1,2-dioleoyl-sn-glycero-3-phospho-L-serine OT - 1,2-dioleoyl-sn-glycero-3-phosphocholine OT - 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine OT - 1,2-dipalmitoyl-sn-glycero-3-phosphocholine OT - 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine OT - Aggregation kinetics OT - Amyloid OT - CD OT - Chol OT - DHPC OT - DMPC OT - DMSO OT - DOPC OT - DOPE OT - DOPG OT - DOPS OT - DPC OT - DPPC OT - Fibril morphology OT - HFIP OT - IAPP OT - LUV OT - Model membranes (LUV SUV, bicelles, micelles) OT - POPC OT - Phospholipid OT - SDS OT - SM OT - ThT OT - Thioflavin T OT - cholesterol OT - circular dichroism OT - dimethyl sulfoxide OT - dodecyl phosphocholine OT - human Islet Amyloid Polypeptide OT - large unilamellar vesicle OT - sodium dodecyl sulphate OT - sphingomyelin EDAT- 2013/05/28 06:00 MHDA- 2013/08/28 06:00 CRDT- 2013/05/28 06:00 PHST- 2012/10/31 00:00 [received] PHST- 2013/04/26 00:00 [revised] PHST- 2013/05/13 00:00 [accepted] PHST- 2013/05/28 06:00 [entrez] PHST- 2013/05/28 06:00 [pubmed] PHST- 2013/08/28 06:00 [medline] AID - S0005-2736(13)00160-0 [pii] AID - 10.1016/j.bbamem.2013.05.014 [doi] PST - ppublish SO - Biochim Biophys Acta. 2013 Sep;1828(9):2091-8. doi: 10.1016/j.bbamem.2013.05.014. Epub 2013 May 23.