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Lipids as Anchors01:32

Lipids as Anchors

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In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
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Phosphoinositides and PIPs01:42

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.
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Membrane Fluidity01:26

Membrane Fluidity

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Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
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Asymmetric Lipid Bilayer01:35

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Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
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Membrane Lipids01:32

Membrane Lipids

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Lipids are an essential component of all biological membranes. The average lipid content in mammalian membranes is 50%, though it can be as low as 20% in the inner mitochondrial membrane or as high as 80% in the myelin sheath present around the nerve cells.
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PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
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Lipid headgroups modulate membrane insertion of pHLIP peptide.

Alexander Kyrychenko1, Victor Vasquez-Montes1, Martin B Ulmschneider2

  • 1Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas.

Biophysical Journal
|February 19, 2015
PubMed
Summary

Lipid composition controls how the pH low insertion peptide (pHLIP) interacts with cell membranes. Modifying lipids can alter pHLIP binding and insertion, offering new strategies for targeted drug delivery.

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Area of Science:

  • Biochemistry
  • Membrane Biophysics
  • Drug Delivery Systems

Background:

  • The pH low insertion peptide (pHLIP) transitions between soluble and membrane-bound states based on pH.
  • pHLIP is a promising tool for drug delivery and imaging acidic tissues like tumors.

Purpose of the Study:

  • To investigate how altering lipid composition affects pHLIP's membrane interaction and insertion.
  • To understand the role of electrostatic interactions in pHLIP conformational changes.

Main Methods:

  • Utilized phosphatidylcholine membranes with varying lipid compositions (anionic lipids, cholesterol, phosphoethanolamine).
  • Observed pHLIP binding and insertion states using biophysical techniques.

Main Results:

  • Anionic lipids, cholesterol, or phosphoethanolamine prevented pHLIP membrane binding at neutral pH.
  • Increased anionic lipid content raised the pKa for pHLIP insertion, indicating modulated protonation and insertion.

Conclusions:

  • Membrane lipid composition significantly influences pHLIP's pH-dependent conformational switching.
  • Tailoring lipid environments offers a method to control pHLIP insertion for therapeutic applications.