Cellular and endosomal lipid bilayer

The cellular and endosomal lipid bilayer is a fundamental structural component of eukaryotic cells, consisting of a double layer of phospholipids interspersed with proteins and cholesterol (Alberts B, et al., Molecular Biology of the Cell, 2002). It serves as a semi-permeable barrier that regulates the passage of ions and molecules, facilitates signal transduction, and manages vesicle-mediated transport such as endocytosis and exocytosis. In modern pharmacology, these membranes are critical targets for advanced drug delivery systems, particularly lipid nanoparticles (LNPs) used in mRNA vaccines and siRNA therapies, which must interact with and escape the endosomal membrane to release their genetic cargo into the cytoplasm (Sahay G, et al., Nature Biotechnology, 2013). Beyond delivery, the lipid bilayer is a direct target for several classes of therapeutics. Certain antimicrobial and antifungal agents, such as Daptomycin and Amphotericin B, exert their effects by directly disrupting the integrity of these bilayers or by binding to specific lipid components like ergosterol (StatPearls, Daptomycin; PubChem CID 5280965). Furthermore, the dysregulation of membrane composition and trafficking is a hallmark of various pathologies, including viral entry mechanisms (e.g., SARS-CoV-2 utilizing endosomal pathways), cancer progression involving altered lipid metabolism, and lysosomal storage disorders where membrane recycling is impaired (Coutinho A, et al., Frontiers in Cell and Developmental Biology, 2021).

Other names

Plasma membraneEndosomal membranePhospholipid bilayerBiological membraneCytoplasmic membrane

Drugs and delivery systems targeting the lipid bilayer typically act through membrane disruption, pore formation, or by facilitating endosomal escape. Lipid nanoparticles (LNPs) utilize ionizable lipids that become protonated in the acidic environment of the endosome, promoting membrane fusion or destabilization to release cargo into the cytosol (Sahay G, et al., Nature Biotechnology, 2013). Antimicrobial agents like Daptomycin aggregate within the membrane to create holes, causing ion leakage and cell death (StatPearls, Daptomycin).