Acidic cell membrane lipid bilayer

The acidic cell membrane lipid bilayer is a distinct physiological feature of the tumor microenvironment, characterized by a lower extracellular pH (pHe) compared to healthy tissues. This acidity is primarily a result of the Warburg effect, where cancer cells exhibit increased glycolysis and lactic acid secretion even in the presence of oxygen (Webb et al., 2011, Nature Reviews Cancer). Additionally, cancer cells often lose the normal asymmetry of their lipid bilayer, leading to the externalization of anionic phospholipids like phosphatidylserine, which further contributes to the acidic or negatively charged nature of the cell surface (Birge et al., 2016, Cell Death & Differentiation). This unique environment serves as a selective target for pH-sensitive therapeutic agents, such as pH-Low Insertion Peptides (pHLIPs), which undergo a conformational change and insert into the membrane only under acidic conditions (Reshetnyak et al., 2006, PNAS). By exploiting this physical property, researchers can deliver imaging agents, toxins, or nucleic acids specifically to malignant cells while minimizing damage to healthy tissues at physiological pH. Beyond oncology, this target is relevant in other pathological states involving acidosis, including inflammation, ischemia, and certain infections.

Other names

Acidic tumor cell membraneAnionic cell membraneAcidic cell surfacePhosphatidylserine-exposed membrane

pH-dependent transmembrane insertion of peptides and selective binding to externalized anionic phospholipids