000218638 001__ 218638
000218638 005__ 20181205220209.0
000218638 0247_ $$2doi$$a10.5075/epfl-thesis-7037
000218638 02470 $$2urn$$aurn:nbn:ch:bel-epfl-thesis7037-4
000218638 02471 $$2nebis$$a10657716
000218638 037__ $$aTHESIS
000218638 041__ $$aeng
000218638 088__ $$a7037
000218638 245__ $$aDiscriminative adsorption of amphiphilic monolayer protected gold nanoparticles on amyloid fibers
000218638 269__ $$a2016
000218638 260__ $$aLausanne$$bEPFL$$c2016
000218638 300__ $$a159
000218638 336__ $$aTheses
000218638 502__ $$aProf. Heinrich Hofmann (président) ; Prof. Francesco Stellacci (directeur de thèse) ; Prof. Hilal Lashuel, Prof. Lucia Pasquato, Prof. Tuomas Knowles (rapporteurs)
000218638 520__ $$aThis thesis presents a systematic study of how different types monolayer-protected AuNPs interact with amyloid fibers. We report a class of amphiphilic gold nanoparticles capable of adsorbing onto specific surface features on these types of protein fibers. A common disease-associated protein fold is the amyloid state: it is characterized by a cross-beta sheet structure that forces proteins and peptides into a fibrillar state, commonly found in illnesses such as Alzheimer’s disease, Parkinson’s disease among many others. Amyloid diseases are typically chronic, correlated with ageing and have posed several challenges: the exact structure of the fibers is difficult to determine and their etiologic role is often unclear. This thesis shows, for the first time, that amphiphilic monolayer-protected AuNPs can discriminatively adsorb onto surface features of amyloid fibers made of A1-40 and -synuclein in vitro and that hydrophobicity determines adsorption onto Tau fibers. Given an amyloid fiber that adopts a twisted ribbon morphology, AuNPs protected by a mixture of sulfonated and hydrophobic thiolate molecules adsorb onto specific features on the surface of the fiber, leaving other interfaces uncovered. This generates a novel supra-molecular assembly that directly interfaces an engineered nanomaterial with a biological structure, without using antibodies. Experiments and calculations demonstrated the importance of nanoparticle size and ligand-shell composition: a size cut-off around 4 nm was observed and other types of water soluble nanoparticles did not adsorb discriminatively. Small amphiphilic AuNPs act as surfactants and probably adsorb onto solvent-exposed beta sheets and small amyloidogenic oligomers. The results presented in this thesis provide a systematic framework to understand the interaction between nanoparticles and amyloid fibers. The particles can, moreover, become useful markers for amyloid research and possibly a cross-instrumental probe to reconcile spectroscopic and imaging techniques to help molecular structure determination. During this work, the synthesis and purification of large amounts of sulfonated thiolate molecules was systematized to generate libraries of differently coated water soluble gold nanoparticles (AuNPs). This helped elucidate how amphiphilic AuNPs fuse with lipid bilayers.
000218638 6531_ $$agold nanoparticles
000218638 6531_ $$aamyloid
000218638 6531_ $$alipid bilayers
000218638 6531_ $$aproteins
000218638 6531_ $$aaggregation
000218638 6531_ $$amonolayer-protected
000218638 6531_ $$amixed-ligand
000218638 6531_ $$aamphiphilic
000218638 6531_ $$abeta sheets
000218638 700__ $$0245275$$aJacob Silva, Paulo Henrique$$g206577
000218638 720_2 $$0244724$$aStellacci, Francesco$$edir.$$g196998
000218638 8564_ $$s72118172$$uhttps://infoscience.epfl.ch/record/218638/files/EPFL_TH7037.pdf$$yn/a$$zn/a
000218638 909C0 $$0252323$$pSUNMIL$$xU12173
000218638 909CO $$ooai:infoscience.tind.io:218638$$pthesis-bn2018$$pDOI$$pSTI$$pthesis$$qDOI2
000218638 917Z8 $$x108898
000218638 917Z8 $$x108898
000218638 918__ $$aSTI$$cIMX$$dEDMX
000218638 919__ $$aSUNMIL
000218638 920__ $$a2016-6-6$$b2016
000218638 970__ $$a7037/THESES
000218638 973__ $$aEPFL$$sPUBLISHED
000218638 980__ $$aTHESIS