title: Insights into the interaction of the N-terminal amyloidogenic polypeptide of ApoA-I with model cellular membranes.
abstract: BACKGROUND
  About twenty variants of apolipoprotein A-I (ApoA-I) are associated to hereditary systemic amyloidoses. Although the molecular bases of this disease are still largely unknown, it has been hypothesized that ApoA-I proteolysis is a key event in pathogenesis, since it triggers the release of an N-terminal fragment (80-100 residue long) that misfolds to form amyloid deposits in peripheral organs and tissues. It is also known that cell membrane lipids play a key role in the fibrillogenic pathway. In the case of ApoA-I related amyloidosis caused by L174S mutation, the 93-residue N-terminal fragment of ApoA-I ([1-93]ApoA-I) was found to be the major constituent of ex vivo fibrils.
  
  
  METHODS
  With the main goal to investigate the interaction of either [1-93]ApoA-I and ApoA-I with biomimetic membranes, we set-up an experimental system based on the Raman Tweezers methodology. We tested GUVs composed by two types of zwitterionic lipids with a different fluidity degree, i.e. dioleoylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC).
  
  
  RESULTS
  We found that [1-93]ApoA-I induces conformational disorder in an ordered lipid bilayer. When interacting with fluid phases, instead, the fragment was found to be able to penetrate the membrane bilayer inducing an alignment of lipid chains.
  
  
  CONCLUSIONS
  The interaction features of [1-93]ApoA-I with biomimetic membranes strongly depend on the lipid phase. Full-length ApoA-I was found to have similar effects, even if significantly less pronounced.
  
  
  CONCLUSIONS
  Our observations shed light on still largely unknown molecular bases of ApoA-I fibrillogenic domain interaction with membranes.
authors.affiliation: Department of Physics E. Pancini, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy. Electronic address: giulia.rusciano@unina.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Rusciano
authors.affiliation: Department of Physics E. Pancini, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pesce
authors.affiliation: Department of Physics E. Pancini, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zito
authors.affiliation: Department of Physics E. Pancini, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sasso
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Gaglione
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Del Giudice
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy; INBB, Istituto Nazionale di Biostrutture e Biosistemi, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Piccoli
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy; INBB, Istituto Nazionale di Biostrutture e Biosistemi, Italy.
authors.forename: Daria Maria
authors.initials: DM
authors.lastname: Monti
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, 80126-I, Naples, Italy; INBB, Istituto Nazionale di Biostrutture e Biosistemi, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Arciello
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry* / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D000682:Amyloid; D016632:Apolipoprotein A-I; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C017251:1,2-oleoylphosphatidylcholine
keywords: Amyloidosis; ApoA-I; Lipid phases; Model membranes; Raman tweezers