Cell membranes and associated anionic surface components

Cell membranes and associated anionic surface components represent a broad class of structural targets primarily utilized by antimicrobial and certain anticancer therapies. In bacteria, these components include lipopolysaccharides (LPS) in Gram-negative species and teichoic acids or phosphatidylglycerol in Gram-positive species, which provide a net negative charge that attracts cationic antimicrobial peptides and lipopeptides [1, 2]. In the context of oncology, the loss of membrane asymmetry leads to the exposure of anionic phospholipids like phosphatidylserine (PS) on the outer leaflet of the plasma membrane, serving as a marker for apoptosis or a target for therapeutic antibodies [3]. Drugs targeting these components typically act by disrupting the physical integrity of the lipid bilayer, leading to cytoplasmic leakage, loss of membrane potential, and eventual cell death [4]. While effective, targeting these ubiquitous structures can lead to significant safety concerns, such as nephrotoxicity and neurotoxicity, due to potential cross-reactivity with host cell membranes [1, 5]. Additionally, these anionic surfaces are exploited in diagnostic imaging, where molecules like Annexin V are used to detect the exposed phosphatidylserine characteristic of apoptotic cells [3].

Other names

Bacterial cell membraneAnionic phospholipidsPhosphatidylserine-rich membranesLipopolysaccharide (LPS)Teichoic acids

Drugs targeting these components typically act through electrostatic attraction to anionic sites, followed by insertion into the lipid bilayer, which causes physical disruption, pore formation, and rapid depolarization of the cell membrane [1, 2, 4].