Anionic cell membrane

The anionic cell membrane is a fundamental physiological target characterized by a net negative surface charge, which distinguishes many bacteria and cancer cells from healthy mammalian cells (Zasloff, 2002, Nature). In prokaryotes, this charge is primarily due to anionic phospholipids like phosphatidylglycerol, while in cancer cells, it often results from the externalization of phosphatidylserine and increased sialic acid expression (Riedl et al., 2011, Biochimica et Biophysica Acta). Cationic antimicrobial and oncolytic peptides exploit this difference, using electrostatic forces to selectively bind and disrupt the lipid bilayer (Hoskin & Ramamoorthy, 2008, Biochimica et Biophysica Acta). This disruption typically leads to rapid loss of membrane integrity, leakage of cytoplasmic contents, and cell death (Melo et al., 2009, Nature Reviews Microbiology). Because the target is a structural component of the cell rather than a specific protein, it offers a broad-spectrum mechanism that is less susceptible to common resistance pathways. However, achieving high selectivity to minimize off-target effects on zwitterionic host membranes remains a primary challenge in drug development (Yeaman & Yount, 2003, Pharmacological Reviews).

Other names

Negatively charged cell membraneAnionic lipid bilayerBacterial cell membraneCancer cell membranePhosphatidylserine-exposed membrane

Therapeutic agents target anionic membranes through initial electrostatic attraction between cationic groups on the drug and negatively charged lipids (e.g., phosphatidylglycerol or phosphatidylserine), followed by membrane insertion and physical disruption via pore formation or lysis (Brogden, 2005, Nature Reviews Microbiology).