membranepermeable

Membranepermeable, often written membrane-permeable, is an adjective describing a substance's ability to cross cellular membranes, particularly the lipid bilayer of the plasma membrane, without requiring specific transporter proteins. This property is central to how compounds reach intracellular targets and how dyes or drugs can be delivered into cells.

Permeability across membranes is determined by physicochemical properties and the cellular environment. The primary route is passive diffusion: small, nonpolar, and lipophilic molecules tend to distribute across membranes more readily. Ionized or highly polar species, and larger molecules, generally have lower intrinsic permeability at physiological pH. The ionization state, governed by pKa and the pH of the surrounding medium, strongly influences diffusion, since uncharged forms diffuse more easily than charged ones. Hydrogen bonding capacity, molecular size, and polar surface area also affect membrane traversal. Some compounds may cross membranes via transporters or channels, which can enhance or regulate their effective permeability.

Examples and scope vary. Gases such as O2 and CO2, small uncharged organic molecules, and many hydrophobic compounds are membrane-permeable. Water is permeable across membranes, primarily through aquaporins, and ethanol diffuses readily. By contrast, ions and large polar molecules are typically membrane-impermeable unless assisted by specific transport mechanisms or prodrugs designed to cross membranes and be activated intracellularly.

Applications include pharmacology and cell biology, where membrane-permeable drugs, probes, and prodrugs are used to achieve intracellular access. Permeability is commonly assessed with assays such as PAMPA or Caco-2, reflecting a compound’s tendency to cross membranes under defined conditions. Permeability is context-dependent, varying with membrane composition, pH, and the presence of transport systems.