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

Luchini, Alessandra, Nzulumike, Achebe N.O., Lind, Tania K., Nylander, Tommy, Barker, Robert, Arleth, Lise, Mortensen, Kell, Cárdenas, Marité (2019) Towards biomimics of cell membranes: Structural effect of phosphatidylinositol triphosphate (PIP3) on a lipid bilayer. Colloids and Surfaces B: Biointerfaces, 173 . pp. 202-209. ISSN 0927-7765. (doi:10.1016/j.colsurfb.2018.09.031) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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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'-myoinositol-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 SLB and the location of DOPIP3 in the lipid membrane. Specifically, QCMD 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.

Item Type: Article
DOI/Identification number: 10.1016/j.colsurfb.2018.09.031
Uncontrolled keywords: Phosphoinositides, supported lipid bilayers, neutron reflectometry
Subjects: Q Science
Divisions: Faculties > Sciences > School of Physical Sciences > Functional Materials Group
Depositing User: Robert Barker
Date Deposited: 15 Oct 2018 13:14 UTC
Last Modified: 12 Jul 2019 10:41 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/69571 (The current URI for this page, for reference purposes)
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