Protein misfolded oligomers are considered the most toxic species amongst those formed in the process of amyloid formation and the molecular basis of their toxicity, although not completely understood, is thought to originate from the interaction with the cellular membrane. Here, we sought to highlight the molecular determinants of oligomer-membrane interaction by atomic force microscopy. We monitored the interaction between multiphase supported lipid bilayers and two types of HypF-N oligomers displaying different structural features and cytotoxicities. By our approach we imaged with unprecedented resolution the ordered and disordered lipid phases of the bilayer and different oligomer structures interacting with either phase. We identified the oligomers and lipids responsible for toxicity and, more generally, we established the importance of the membrane lipid component in mediating oligomer toxicity. Our findings support the importance of GM1 ganglioside in mediating the oligomer-bilayer interaction and support a mechanism of oligomer cytotoxicity involving bilayer destabilization by globular oligomers within GM1-rich ordered raft regions rather than by annular oligomers in the surrounding disordered membrane domains.

Interaction of toxic and non-toxic HypF-N oligomers with lipid bilayers investigated at high resolution with atomic force microscopy / Oropesa-Nuñez, R; Seghezza, S; Dante, S; Diaspro, A; Cascella, R; Cecchi, C; Stefani, M; Chiti, F; Canale, C. - In: ONCOTARGET. - ISSN 1949-2553. - STAMPA. - 7:(2016), pp. 44991-45004.

Interaction of toxic and non-toxic HypF-N oligomers with lipid bilayers investigated at high resolution with atomic force microscopy

CASCELLA, ROBERTA;CECCHI, CRISTINA;STEFANI, MASSIMO;CHITI, FABRIZIO;
2016

Abstract

Protein misfolded oligomers are considered the most toxic species amongst those formed in the process of amyloid formation and the molecular basis of their toxicity, although not completely understood, is thought to originate from the interaction with the cellular membrane. Here, we sought to highlight the molecular determinants of oligomer-membrane interaction by atomic force microscopy. We monitored the interaction between multiphase supported lipid bilayers and two types of HypF-N oligomers displaying different structural features and cytotoxicities. By our approach we imaged with unprecedented resolution the ordered and disordered lipid phases of the bilayer and different oligomer structures interacting with either phase. We identified the oligomers and lipids responsible for toxicity and, more generally, we established the importance of the membrane lipid component in mediating oligomer toxicity. Our findings support the importance of GM1 ganglioside in mediating the oligomer-bilayer interaction and support a mechanism of oligomer cytotoxicity involving bilayer destabilization by globular oligomers within GM1-rich ordered raft regions rather than by annular oligomers in the surrounding disordered membrane domains.
2016
7
44991
45004
Oropesa-Nuñez, R; Seghezza, S; Dante, S; Diaspro, A; Cascella, R; Cecchi, C; Stefani, M; Chiti, F; Canale, C
File in questo prodotto:
File Dimensione Formato  
Oropesa 2016 Oncotarget.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 4.35 MB
Formato Adobe PDF
4.35 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1075157
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 22
social impact