Cellular membranes and associated macromolecules

Cellular membranes are dynamic, semi-permeable barriers composed of a phospholipid bilayer, cholesterol, and various embedded macromolecules such as proteins and carbohydrates. They are essential for maintaining cellular homeostasis, facilitating signal transduction, and enabling selective transport of ions and molecules (Alberts B, et al. Molecular Biology of the Cell, 2002) [1]. While most drugs target specific membrane proteins like receptors or channels, some therapeutic agents target the membrane structure itself. For instance, polymyxin antibiotics and lipopeptides like daptomycin disrupt bacterial membrane integrity to treat multi-drug resistant infections (StatPearls, 2023; PubMed, PMID: 15138441) [2, 4]. Similarly, polyene antifungals like amphotericin B target membrane sterols to induce pore formation (PubChem, CID 5280965) [3]. However, targeting the membrane directly presents significant safety challenges, as the lack of high specificity can lead to host cell damage, resulting in side effects such as nephrotoxicity or hemolysis. This target entry is considered broad and non-specific, as it encompasses a wide array of distinct molecular entities and structural components.

Other names

Plasma membraneBiological membraneLipid bilayerCell membraneCytoplasmic membrane

Drugs targeting cellular membranes typically act through physical disruption of the lipid bilayer, formation of transmembrane pores, or alteration of membrane fluidity and electrochemical gradients. For example, lipopeptide antibiotics like daptomycin insert into the bacterial membrane in a calcium-dependent manner to cause rapid depolarization (PubMed, PMID: 15138441) [4]. Polyene antifungals like amphotericin B bind to ergosterol in fungal membranes to create lethal pores (PubChem, CID 5280965) [3], while polymyxins interact with lipopolysaccharides to disrupt the outer membrane of Gram-negative bacteria (StatPearls, Polymyxin B, 2023) [2].