Calcium-dependent anionic phospholipid membrane

Phospholipid membranes in the presence of calcium ions (Ca2+) function as a critical pharmacological target, particularly for lipopeptide antibiotics and apoptosis-sensing proteins. In bacterial cells, the presence of Ca2+ is essential for the binding of daptomycin to anionic phospholipids like phosphatidylglycerol; the calcium ions neutralize electrostatic repulsion, allowing the drug to insert into the membrane and cause lethal depolarization (Muller et al., 2016, Nature Communications). In mammalian physiology, the exposure of phosphatidylserine on the outer leaflet of the plasma membrane in a Ca2+-dependent manner is a hallmark of apoptosis and provides a scaffold for the assembly of coagulation factors (Zwaal et al., 2005, Blood). This calcium-lipid interface is exploited by diagnostic agents such as Annexin A5, which binds specifically to these sites to image cell death in oncology and cardiovascular diseases (Gerke et al., 2005, Nature Reviews Molecular Cell Biology). Consequently, this target is central to the treatment of multi-drug resistant Gram-positive infections and the monitoring of various pathological states involving membrane remodeling.

Other names

Phospholipid membranes in the presence of Ca2+Ca2+-phospholipid complexAnionic phospholipid bilayerPhosphatidylglycerol-calcium complexPhosphatidylserine-calcium complex

Calcium ions facilitate the binding of specific drugs or proteins to anionic phospholipids by forming a coordination complex that bridges the negatively charged ligand and the lipid headgroups, leading to membrane insertion, pore formation, or signaling initiation.