Macromolecules such as proteins, polysaccharides, and nucleic acids are simply too large and too charged or polar to pass through biological membranes. This is actually fortunate—think of the consequences if such molecules diffused out of cells: A red blood cell would not retain its hemoglobin! As you saw in Chapter 5, the development of a selectively permeable membrane was essential for the functioning of the first cells when life on Earth began. The interior of a cell can be maintained as a separate compartment with a different composition from that of the exterior environment, which is subject to abrupt changes. However, cells must sometimes take up or secrete (release to the external environment) intact large molecules. In Key Concept 5.3 we described phagocytosis, the mechanism by which solid particles can be brought into the cell by means of vesicles that pinch off from the cell membrane. The general terms for the mechanisms by which substances enter and leave the cell via membrane vesicles are endocytosis and exocytosis.