Endosomal membrane phospholipid bilayer

The endosomal membrane phospholipid bilayer is a dynamic lipid structure that defines the boundary of endocytic vesicles, playing a central role in the sorting, trafficking, and degradation of internalized proteins and lipids (Gruenberg, J., 2020, Nature Reviews Molecular Cell Biology). It is characterized by a unique lipid composition, including phosphoinositides and bis(monoacylglycero)phosphate, which regulate the recruitment of various cytosolic proteins involved in membrane remodeling and fusion. In the context of infectious diseases, many viruses exploit the endosomal membrane as a site for cell entry, relying on the acidic luminal environment to trigger conformational changes in viral proteins that lead to membrane fusion (Hu, T. Y., et al., 2020, International Journal of Antimicrobial Agents). Pharmacological intervention often involves the use of lysosomotropic weak bases that accumulate in the endosome, raising the pH and thereby inhibiting viral entry or altering protein processing. Additionally, the endosomal membrane represents a major barrier for the delivery of macromolecular drugs, such as mRNA and siRNA, leading to the development of delivery systems designed to destabilize the bilayer and promote endosomal escape (Smith, S. A., et al., 2019, Bioconjugate Chemistry).

Other names

Endosomal membraneEndosomal lipid bilayerEndocytic membrane

Drugs targeting the endosomal membrane typically act by increasing endosomal pH to inhibit pH-dependent viral fusion, or by physically disrupting the bilayer to facilitate the escape of therapeutic molecules into the cytosol.