General cell and endosomal membranes

General cell and endosomal membranes are fundamental lipid bilayer structures that define the boundaries of the cell and its internal compartments. The plasma membrane regulates the exchange of substances with the extracellular environment and serves as a scaffold for signaling complexes [1]. Endosomal membranes are dynamic structures involved in the sorting and trafficking of proteins and lipids internalized from the cell surface [2]. These membranes are primarily composed of a variety of phospholipids, cholesterol, and integral membrane proteins that maintain structural integrity and facilitate transport [3]. In pharmacology, these membranes are targeted by diverse agents, including lysosomotropic drugs like chloroquine that alter endosomal pH to inhibit viral entry, and antimicrobial peptides that disrupt pathogen membrane integrity [4][5]. Additionally, the endosomal membrane is a critical barrier for the delivery of modern therapeutics such as mRNA-loaded lipid nanoparticles, which require efficient endosomal escape to reach the cytosol [6]. Because these membranes are ubiquitous across all human tissues, achieving therapeutic selectivity remains a major challenge in drug development [7]. References: [1] Alberts B, et al. Molecular Biology of the Cell (2014); [2] Huotari J & Helenius A. EMBO J (2011); [3] van Meer G, et al. Nat Rev Mol Cell Biol (2008); [4] Al-Bari MA. Fundam Clin Pharmacol (2017); [5] Epand RM. Biochim Biophys Acta (2016); [6] Zhang S, et al. Acc Chem Res (2019); [7] Nelson AR, et al. J Control Release (2020).

Other names

Plasma membraneEndosomal membraneLipid bilayerCellular membrane systemCytoplasmic membrane

Drugs interacting with these structures typically function through membrane disruption, pore formation, or by modulating the internal pH of endosomal compartments (lysosomotropic effect) to interfere with viral replication or facilitate the endosomal escape of therapeutic payloads.