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Towards biomimics of cell membranes : Structural effect of phosphatidylinositol triphosphate (PIP3) on a lipid bilayer

Luchini, Alessandra; Nzulumike, Achebe N.O.; Lind, Tania K. LU ; Nylander, Tommy LU ; Barker, Robert; Arleth, Lise; Mortensen, Kell and Cárdenas, Marité LU (2019) In Colloids and Surfaces B: Biointerfaces 173. p.202-209
Abstract

Phosphoinositide (PIP) lipids are anionic phospholipids playing a fundamental role for the activity of several transmembrane and soluble proteins. Among all, phosphoinositol-3′,4′,5′-trisphosphate (PIP3) is a secondary signaling messenger that regulates the function of proteins involved in cell growth and gene transcription. The present study aims to reveal the structure of PIP-containing lipid membranes, which so far has been little explored. For this purpose, supported lipid bilayers (SLBs) containing 1,2-dioleoyl-sn-glycero-3-phospho-(1′-myo-inositol-3′,4′,5′-trisphosphate (DOPIP3) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were used as mimics of biomembranes. Surface sensitive techniques, i.e.... (More)

Phosphoinositide (PIP) lipids are anionic phospholipids playing a fundamental role for the activity of several transmembrane and soluble proteins. Among all, phosphoinositol-3′,4′,5′-trisphosphate (PIP3) is a secondary signaling messenger that regulates the function of proteins involved in cell growth and gene transcription. The present study aims to reveal the structure of PIP-containing lipid membranes, which so far has been little explored. For this purpose, supported lipid bilayers (SLBs) containing 1,2-dioleoyl-sn-glycero-3-phospho-(1′-myo-inositol-3′,4′,5′-trisphosphate (DOPIP3) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were used as mimics of biomembranes. Surface sensitive techniques, i.e. Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), Atomic Force Microscopy (AFM) and Neutron Reflectometry (NR), provided detailed information on the formation of the SLB and the location of DOPIP3 in the lipid membrane. Specifically, QCM-D and AFM were used to identify the best condition for lipid deposition and to estimate the total bilayer thickness. On the other hand, NR was used to collect experimental structural data on the DOPIP3 location and orientation within the lipid membrane. The two bilayer leaflets showed the same DOPIP3 concentration, thus suggesting the formation of a symmetric bilayer. The headgroup layer thicknesses of the pure POPC and the mixed POPC/DOPIP3 bilayer suggest that the DOPIP3-headgroups have a preferred orientation, which is not perpendicular to the membrane surface, but instead it is close to the surrounding lipid headgroups. These results support the proposed PIP3 tendency to interact with the other lipid headgroups as PC, so far exclusively suggested by MD simulations.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Neutron Reflectometry, Phosphoinositides, Supported lipid bilayers
in
Colloids and Surfaces B: Biointerfaces
volume
173
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85054307725
ISSN
0927-7765
DOI
10.1016/j.colsurfb.2018.09.031
language
English
LU publication?
yes
id
7a2ceb33-f093-411a-9c4b-6c4806b8c37a
date added to LUP
2018-10-26 13:01:01
date last changed
2018-11-13 10:55:28
@article{7a2ceb33-f093-411a-9c4b-6c4806b8c37a,
  abstract     = {<p>Phosphoinositide (PIP) lipids are anionic phospholipids playing a fundamental role for the activity of several transmembrane and soluble proteins. Among all, phosphoinositol-3′,4′,5′-trisphosphate (PIP<sub>3</sub>) is a secondary signaling messenger that regulates the function of proteins involved in cell growth and gene transcription. The present study aims to reveal the structure of PIP-containing lipid membranes, which so far has been little explored. For this purpose, supported lipid bilayers (SLBs) containing 1,2-dioleoyl-sn-glycero-3-phospho-(1′-myo-inositol-3′,4′,5′-trisphosphate (DOPIP<sub>3</sub>) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were used as mimics of biomembranes. Surface sensitive techniques, i.e. Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), Atomic Force Microscopy (AFM) and Neutron Reflectometry (NR), provided detailed information on the formation of the SLB and the location of DOPIP<sub>3</sub> in the lipid membrane. Specifically, QCM-D and AFM were used to identify the best condition for lipid deposition and to estimate the total bilayer thickness. On the other hand, NR was used to collect experimental structural data on the DOPIP<sub>3</sub> location and orientation within the lipid membrane. The two bilayer leaflets showed the same DOPIP<sub>3</sub> concentration, thus suggesting the formation of a symmetric bilayer. The headgroup layer thicknesses of the pure POPC and the mixed POPC/DOPIP<sub>3</sub> bilayer suggest that the DOPIP<sub>3</sub>-headgroups have a preferred orientation, which is not perpendicular to the membrane surface, but instead it is close to the surrounding lipid headgroups. These results support the proposed PIP<sub>3</sub> tendency to interact with the other lipid headgroups as PC, so far exclusively suggested by MD simulations.</p>},
  author       = {Luchini, Alessandra and Nzulumike, Achebe N.O. and Lind, Tania K. and Nylander, Tommy and Barker, Robert and Arleth, Lise and Mortensen, Kell and Cárdenas, Marité},
  issn         = {0927-7765},
  keyword      = {Neutron Reflectometry,Phosphoinositides,Supported lipid bilayers},
  language     = {eng},
  pages        = {202--209},
  publisher    = {Elsevier},
  series       = {Colloids and Surfaces B: Biointerfaces},
  title        = {Towards biomimics of cell membranes : Structural effect of phosphatidylinositol triphosphate (PIP<sub>3</sub>) on a lipid bilayer},
  url          = {http://dx.doi.org/10.1016/j.colsurfb.2018.09.031},
  volume       = {173},
  year         = {2019},
}