Bacterial and tumor cell lipid membranes

Bacterial and tumor cell lipid membranes are essential biological barriers that serve as therapeutic targets due to their distinct anionic surface charge compared to healthy mammalian cells (Epand et al., 2016, PMID: 27532837). While healthy cells primarily feature zwitterionic lipids on their outer leaflet, bacterial membranes are rich in negatively charged lipids like phosphatidylglycerol, and many cancer cells expose anionic phosphatidylserine on their outer surface (Riedl et al., 2011, PMID: 21633955). This negative charge allows for the selective recruitment of cationic antimicrobial peptides (AMPs) and synthetic mimics through electrostatic interactions (Mahlapuu et al., 2016, PMID: 27000434). Once bound, these agents typically insert into the lipid bilayer, causing physical disruption, pore formation, or depolarization, which leads to rapid cell death (Hancock & Sahl, 2006, PMID: 16467831). Targeting the membrane is particularly advantageous as it is a fundamental structural component, making the development of resistance more difficult compared to protein-specific targets (Zasloff, 2002, PMID: 11807545). However, maintaining selectivity to avoid hemolysis and nephrotoxicity remains a significant therapeutic challenge (Landman et al., 2008, PMID: 18549350).

Other names

Anionic lipid membranesNegatively charged cell membranesBacterial cytoplasmic membranesCancer cell membranesProkaryotic membranes

Disruption of membrane integrity through electrostatic binding to anionic lipids, followed by hydrophobic insertion, leading to pore formation, depolarization, and physical lysis (Hancock & Sahl, 2006, PMID: 16467831).