Negatively charged cell membrane

Negatively charged cell membranes represent a distinct physiological target characterized by an abundance of anionic lipids on the outer leaflet, a feature typically absent in healthy mammalian cells. In normal eukaryotic cells, negatively charged phospholipids like phosphatidylserine (PS) are restricted to the inner leaflet by flippase enzymes, but this asymmetry is disrupted in cancer cells and during apoptosis, leading to an anionic surface (Birge et al., 2016, Nature Reviews Cancer). Furthermore, the cell envelopes of bacteria are inherently negatively charged due to components like lipopolysaccharides in Gram-negative bacteria and teichoic acids in Gram-positive bacteria (Yeaman & Yount, 2003, Pharmacological Reviews). This charge differential allows for the selective targeting of pathogens and malignant cells by cationic therapeutic agents, such as antimicrobial peptides and polymyxins, which bind via electrostatic attraction. Once bound, these agents typically disrupt membrane integrity through pore formation or detergent-like lysis, leading to rapid cell death (Poole et al., 2018, Journal of Antimicrobial Chemotherapy). Because this mechanism targets fundamental physical properties of the membrane rather than specific protein receptors, it is often effective against multi-drug resistant strains.

Other names

Anionic cell membraneAnionic lipid bilayerPhosphatidylserine-exposed membraneAnionic membrane surface

Electrostatic attraction between cationic drug molecules and anionic membrane components (e.g., LPS, teichoic acids, or phosphatidylserine) leading to membrane permeabilization, pore formation, or immune recruitment.