Anionic endosomal membrane phospholipid bilayer (AEMPB)

The anionic endosomal membrane phospholipid bilayer is a specialized lipid structure characterized by a high concentration of negatively charged lipids, most notably bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA). These lipids are primarily localized to the internal membranes of late endosomes and lysosomes, where they play a critical role in regulating membrane docking, fusion, and the degradation of complex lipids and proteins. The unique anionic environment and the acidic lumen of the endosome are essential for the sorting of internalized cargo and the maintenance of cellular homeostasis. In the context of modern therapeutics, this membrane serves as a primary physiological barrier and target for drug delivery systems. Ionizable lipid nanoparticles (LNPs) are designed to become protonated within the acidic endosome, interacting electrostatically with the anionic bilayer to induce membrane hexagonal phase transitions. This process, known as endosomal escape, is the fundamental mechanism by which nucleic acid therapies, such as siRNA and mRNA vaccines, bypass degradative pathways to reach their cytosolic targets. Additionally, alterations in the composition of this bilayer are implicated in lysosomal storage disorders and are exploited by various viruses for cellular entry.

Other names

Endosomal membraneAnionic endosomal lipidsLate endosomal membraneBis(monoacylglycero)phosphate-rich membraneLysobisphosphatidic acid-rich membrane

Drugs, particularly ionizable lipid nanoparticles (LNPs), interact with the anionic phospholipids (such as BMP/LBPA) in the endosomal membrane through electrostatic interactions triggered by the acidic pH of the endosome. This interaction facilitates membrane destabilization and 'endosomal escape,' allowing the therapeutic cargo (e.g., siRNA or mRNA) to be released into the cytosol. Other drugs may bind these lipids to inhibit viral fusion or alter lysosomal lipid processing.