Effect of the HIV-1 fusion peptide on the mechanical properties and leaflet coupling of lipid bilayers

P Shchelokovskyy,S Tristram-Nagle,R Dimova

doi:10.1088/1367-2630/13/2/025004

P Shchelokovskyy, S Tristram-Nagle + Show 1 more

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https://doi.org/10.1088/1367-2630/13/2/025004

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Abstract

The fusion peptide (FP) of the human immunodeficiency virus (HIV) is part of the N-terminus of the viral envelope glycoprotein gp41 and is believed to play an important role in the viral entry process. To understand the immediate effect of this peptide on the cell membrane, we have studied the influence of the synthetic FP sequence FP23 on the mechanical properties of model lipid bilayers. For this purpose, giant unilamellar vesicles were prepared from the unsaturated lipid dioleoylphosphatidylcholine mixed in various molar ratios with FP23. The bending stiffness of the vesicles was measured with two different methods: fluctuation analysis and aspiration with micropipettes. The data obtained from both of these approaches show that the bending stiffness of the membrane decreases gradually with increasing concentration of the FP23 in the bilayer. Low concentrations of only a few mol% FP23 are sufficient to decrease the bending stiffness of the lipid bilayer by about a factor of 2. Finally, data obtained for the stretching elasticity modulus of the membrane suggest that the peptide insertion decreases the coupling between the two leaflets of the bilayer.

Highlights

The human immunodeficiency virus (HIV) uses ectodomain glycoproteins to dock with receptors on the T-cell membrane
Our studies on giant vesicles show that the HIV-1 fusion peptide (FP) lowers the bending rigidity of freely suspended lipid bilayers made of DOPC
These results support earlier studies collected on lipid membrane stacks [19], suggesting coherence of the behaviour of the DOPC–FP23 system on different lengthscales

Summary

Introduction

The human immunodeficiency virus (HIV) uses ectodomain glycoproteins to dock with receptors on the T-cell membrane. It perturbs the target membrane forming a pore [1]. FP23 is reported to have a largely αhelical conformation in HiP and in phosphatidylglycerol–phosphatidylcholine membranes [7, 8]. Populations of both α-helical and β-sheet conformations have been observed for other membrane constructs, with β-sheet favored at higher peptide–lipid molar ratios and in membranes containing cholesterol [8]–[10]. It has even been proposed that conversion from α-helical to β-structure is a step in membrane fusion [12]

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