Membrane phospholipid interface

The membrane phospholipid interface is the chemically complex boundary between the hydrophobic core of the lipid bilayer and the surrounding aqueous environment, characterized by polar head groups, water molecules, and ions (Nature Reviews Molecular Cell Biology, PMID: 18431397). Biologically, it serves as a scaffold for the recruitment of signaling proteins and regulates the function of integral membrane proteins through lateral pressure and electrostatic interactions. In pharmacology, the interface is a primary target for various classes of drugs, particularly antimicrobials like daptomycin and polymyxins, which exploit differences in lipid composition between host and pathogen membranes (Journal of Biological Chemistry, PMID: 24514086). Disruption of this interface can lead to rapid loss of membrane potential and cell death, making it an effective target for treating resistant infections. Furthermore, alterations in the phospholipid interface, such as the externalization of phosphatidylserine, are exploited in cancer therapeutics and imaging (Theranostics, PMID: 21810451). However, the challenge in targeting these interfaces lies in achieving sufficient selectivity to avoid damaging host cell membranes, which can result in side effects such as hemolysis or organ toxicity.

Other names

Lipid bilayer interfacePhospholipid membrane interfaceMembrane-water interfaceCell membrane interface

Drugs targeting the membrane phospholipid interface typically act by disrupting membrane integrity, inducing pore formation, or altering the physical properties (such as fluidity and curvature) of the bilayer to modulate the activity of embedded proteins or cause cell lysis (Nature Reviews Drug Discovery, PMID: 16052241).