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Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

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Related in: MedlinePlus

Lateral pressure profile for a lipid bilayer (left), with surface tension being balanced by steric repulsion between the head-groups and acyl chains. See text for details. Adapted from [51].
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fig05: Lateral pressure profile for a lipid bilayer (left), with surface tension being balanced by steric repulsion between the head-groups and acyl chains. See text for details. Adapted from [51].

Mentions: Intimately related to membrane spontaneous curvature is the lateral pressure profile [76]. This concept is highly useful in understanding of several characteristics of membranes. In brief, approaching the surface of a PC bilayer from the water phase and recording the prevailing forces acting on the lipid assembly, there is first a zone with repulsive potential between the strongly hydrated headgroups, such as for PCs and SMs (Fig. 5). Adjacent to the above there is a zone where the hydrophobic effect manifests as interfacial tension, with hydrophobicity of the lipid hydrocarbon chains restricting their contacts with water molecules. Whenever thermal motion and repulsive interactions increased the exposure of the acyl chains to water, its entropy decreased. The resulting tension balances not only the steric repulsion between the headgroups but also the repulsion between the acyl chains, prevailing in the hydrocarbon region of the bilayer. Because of these forces are acting on very narrow zones, the pressure can be considerable, estimated to be hundreds of atmospheres.


Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Lateral pressure profile for a lipid bilayer (left), with surface tension being balanced by steric repulsion between the head-groups and acyl chains. See text for details. Adapted from [51].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401130&req=5

fig05: Lateral pressure profile for a lipid bilayer (left), with surface tension being balanced by steric repulsion between the head-groups and acyl chains. See text for details. Adapted from [51].
Mentions: Intimately related to membrane spontaneous curvature is the lateral pressure profile [76]. This concept is highly useful in understanding of several characteristics of membranes. In brief, approaching the surface of a PC bilayer from the water phase and recording the prevailing forces acting on the lipid assembly, there is first a zone with repulsive potential between the strongly hydrated headgroups, such as for PCs and SMs (Fig. 5). Adjacent to the above there is a zone where the hydrophobic effect manifests as interfacial tension, with hydrophobicity of the lipid hydrocarbon chains restricting their contacts with water molecules. Whenever thermal motion and repulsive interactions increased the exposure of the acyl chains to water, its entropy decreased. The resulting tension balances not only the steric repulsion between the headgroups but also the repulsion between the acyl chains, prevailing in the hydrocarbon region of the bilayer. Because of these forces are acting on very narrow zones, the pressure can be considerable, estimated to be hundreds of atmospheres.

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

Show MeSH
Related in: MedlinePlus