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How can molecules that cannot penetrate the cellular membrane cause changes within a cell? Many signaling molecules are proteins or other molecules that cannot diffuse across the lipid bilayer of a biological membranes. Signaling molecules called first messengers, are able to affect events inside of cells by reacting with receptor proteins embedded in the lipid bilayer. The animation shows details of how this is accomplished in several specific examples. In every case, the first messenger changes the conformation of the receptor protein. Sometimes this opens a channel through the membrane. In many other cases the conformational change catalyses a chemical reaction inside the cell. The messenger is essentially activating an enzyme, one that is embedded in the membrane. The initial reaction is the first step in a pathway that leads to the cell’s response.