Negatively charged and zwitterionic cell membrane

Negatively charged and zwitterionic cell membranes are the fundamental lipid bilayers that enclose cells and organelles, providing structural integrity and regulating molecular traffic. These membranes are primarily composed of phospholipids, where the specific arrangement of headgroups determines the surface charge; for instance, bacterial membranes are typically rich in negatively charged lipids like phosphatidylglycerol, while mammalian membranes are predominantly zwitterionic on their outer surface (Yeaman & Yount, 2003). This chemical disparity is the basis for the selectivity of various therapeutic agents, such as polymyxins and daptomycin, which preferentially bind to and disrupt anionic bilayers (Brogden, 2005). Upon binding, these drugs insert into the membrane, causing pore formation, depolarization, and eventual cell lysis. In oncology, the exposure of negatively charged phosphatidylserine on the outer leaflet of cancer cells serves as a biomarker and a target for membrane-disrupting anticancer peptides (Riedl et al., 2011). However, the therapeutic use of membrane-targeting drugs is often limited by safety concerns such as hemolysis and nephrotoxicity, arising from insufficient discrimination between pathogen and host cell membranes (Epand & Epand, 2011).

Other names

Lipid bilayerPlasma membraneAnionic and neutral lipid membranesCellular lipid bilayer

The mechanism of action involves the electrostatic attraction of cationic molecules to negatively charged lipid headgroups, followed by hydrophobic insertion into the bilayer core. This leads to membrane thinning and the formation of transmembrane pores through models such as the barrel-stave or toroidal pore, or via a carpet mechanism that results in total membrane disintegration (Brogden, 2005). These disruptions cause the leakage of essential ions and metabolites, leading to the dissipation of the membrane potential and rapid cell death (Yeaman & Yount, 2003).