Abstract

The eukaryotic cell membrane possesses numerous complex functions, which are essential for life. At this, the composition and the structure of the lipid bilayer are of particular importance. Polyunsaturated fatty acids may modulate the physical properties of biological membranes via alteration of membrane lipid composition affecting numerous physiological processes, e.g. in the immune system. In this systematic study we present fatty acid and peptide profiles of cell membrane and membrane rafts of murine macrophages that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. Using fatty acid composition analysis and mass spectrometry-based peptidome profiling we found that PUFAs from both the n-3 and the n-6 family have an impact on lipid and protein composition of plasma membrane and membrane rafts in a similar manner. In addition, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the unsaturation index of plasma membrane as well as membrane rafts of supplemented cells. With regard to the proposed significance of lipid microdomains for disease development and treatment our study will help to achieve a targeted dietary modulation of immune cell lipid bilayers.

Highlights

  • In the last decade the traditional fluid mosaic model of the plasma membrane as introduced 1972 by Singer and Nicholson [1] has been extended to the lipid raft hypothesis [2]

  • Studies concerning the effects of Polyunsaturated fatty acids (PUFAs) from the n-3 family, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on immune cell function proposed a selective displacement of acylated proteins from membrane rafts by virtue of a modified raft lipid environment [11]. In this systematic study we present fatty acid and peptide profiles of plasma membrane and rafts of macrophages from the murine cell line RAW264.7 that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family

  • The differences in the fatty acid profiles of the two membrane domains were reflected by the Methylene Bridge Index (MBI) which was about 3 times greater for plasma membrane than for membrane rafts (Table 1, Table 2)

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Summary

Introduction

In the last decade the traditional fluid mosaic model of the plasma membrane as introduced 1972 by Singer and Nicholson [1] has been extended to the lipid raft hypothesis [2]. According to this structurally and functionally distinct domains can be distinguished within the cell membrane due to their specific lipid compositions [2]. In a Keystone Symposium on Lipid Rafts and Cell Function the resulting microenvironments were defined as ‘‘small (10–200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that compartmentalize cellular processes’’ [3]. Further cellular processes membrane domains have been implicated include membrane trafficking and molecular sorting [7]

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