Cell Membrane
The phospholipid bilayer that forms the boundary of all cells, controlling the passage of substances in and out. Many peptide drugs act on receptors embedded in cell membranes. Antimicrobial peptides (daptomycin, colistin, polymyxin B) kill bacteria by disrupting their cell membranes.
Technical Context
The cell membrane is a phospholipid bilayer (~5nm thick) with embedded and peripheral proteins (fluid mosaic model, Singer-Nicolson 1972). Lipid composition: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine (inner leaflet — externalisation signals apoptosis for phagocyte recognition), sphingomyelin, and cholesterol (modulating fluidity). Membrane functions: selective permeability, receptor-mediated signalling (most peptide drug targets — GPCRs, receptor tyrosine kinases — are integral membrane proteins), cell adhesion, and transport. Antimicrobial peptides exploit membrane differences between bacterial and mammalian cells: bacterial membranes have higher anionic phospholipid content (phosphatidylglycerol, cardiolipin) and no cholesterol, providing the electrostatic selectivity that allows cationic AMPs (defensins, LL-37, polymyxins) to preferentially target bacteria while sparing host cells. Daptomycin's calcium-dependent mechanism specifically targets the bacterial membrane through this selectivity.