The selective permeability of biological membranes to small molecules allows the cell to control and maintain its internal composition. Only small uncharged molecules can diffuse freely through phospholipid bilayers. Small nonpolar molecules, such as O2 and CO2, are soluble in the lipid bilayer and therefore can readily cross cell membranes. Small uncharged polar molecules, such as H2O, also can diffuse through membranes, but larger uncharged polar molecules, such as glucose, cannot. Charged molecules, such as ions, are unable to diffuse through a phospholipid bilayer regardless of size; even H+ ions cannot cross a lipid bilayer by free diffusion.
Although ions and most polar molecules cannot diffuse across a lipid bilayer, many such molecules (such as glucose) are able to cross cell membranes. These molecules pass across membranes via the action of specific transmembrane proteins, which act as transporters. Such transport proteins determine the selective permeability of cell membranes and thus play a critical role in membrane function. They contain multiple membrane-spanning regions that form a passage through the lipid bilayer, allowing polar or charged molecules to cross the membrane through a protein pore without interacting with the hydrophobic fatty acid chains of the membrane phospholipids.