Cells use signaling molecules or ligands for communication. The molecules that serve as cellular signals vary in their chemical and physical properties, as well as their range of action. Chemically, ligands may be ions like calcium, small molecules like the neurotransmitter acetylcholine, or peptides and proteins like growth factors. Dissolved gases like nitric oxide also serve as signals. Additionally, cells respond to physical signals such as light, touch, and heat. Receptor-ligand interactions are central to cellular signaling. Hydrophilic molecules cannot cross the plasma membrane. Many bind to receptors on the cell surface; however, small hydrophilic molecules may be transported across the plasma membrane to an adjacent cell via gap junctions. Hydrophobic molecules, like steroid hormones, can freely diffuse through the cell membrane and bind to intracellular receptors. Signaling molecules can act over long- or short- ranges. Some ligands, such as cytokines, are released by exocytosis into the extracellular space and target distant cells. Whereas membrane-bound ligands, such as integrins, directly bind to receptors on the adjacent cells or to the extracellular matrix.