Functional Systems of the Cell
We discuss several representative functional systems of the cell that make it a living organism.
Ingestion by the Cell—Endocytosis
If a cell is to live and grow and reproduce, it must obtain nutrients and other substances from the surrounding ﬂuids. Most substances pass through the cell membrane by diffusion and active transport. Diffusion involves simple movement through the membrane caused by the random motion of the molecules of the substance; substances move either through cell membrane pores or, in the case of lipid soluble substances, through the lipid matrix of the membrane. Active transport involves the actual carrying of a substance through the membrane by a physical protein structure that penetrates all the way through the membrane. These active transport mechanisms are so important to cell function that they are presented in detail in other article. Very large particles enter the cell by a specialized function of the cell membrane called endocytosis. The principal forms of endocytosis are pinocytosis and phagocytosis. Pinocytosis means ingestion of minute particles that form vesicles of extracellular ﬂuid and particulate constituents inside the cell cytoplasm. Phagocytosis means ingestion of large particles, such as bacteria, whole cells, or portions of degenerating tissue.
Pinocytosis occurs continually in the cell membranes of most cells, but it is especially rapid in some cells. For instance, it occurs so rapidly in macrophages that about 3 per cent of the total macrophage membrane is engulfed in the form of vesicles each minute. Even so, the pinocytotic vesicles are so small usually only 100 to 200 nanometers in diameter that most of them can be seen only with the electron microscope. Pinocytosis is the only means by which most large macromolecules, such as most protein molecules, can enter cells. In fact, the rate at which pinocytotic vesicles form is usually enhanced when such macromolecules attach to the cell membrane. The given diagram demonstrates the successive steps of pinocytosis, showing three molecules of protein attaching to the membrane. These molecules usually attach to specialized protein receptors on the surface of the membrane that are speciﬁc for the type of protein that is to be absorbed. The receptors generally are concentrated in small pits on the outer surface of the cell membrane, called coated pits. On the inside of the cell membrane beneath these pits is a latticework of ﬁbrillar protein called clathrin, as well as other proteins, perhaps including contractile ﬁlaments of actin and myosin. Once the protein molecules have bound with the receptors, the surface properties of the local membrane change in such a way that the entire pit invaginates inward, and the ﬁbrillar proteins surrounding the invaginating pit cause its borders to close over the attached proteins as well as over a small amount of extracellular ﬂuid. Immediately thereafter, the invaginated portion of the membrane breaks away from the surface of the cell, forming a pinocytotic vesicle inside the cytoplasm of the cell. What causes the cell membrane to go through the necessary contortions to form pinocytotic vesicles remains mainly a mystery. This process requires energy from within the cell; this is supplied by ATP, a high energy. Also, it requires the presence of calcium ions in the extracellular ﬂuid, which probably react with contractile protein ﬁlaments beneath the coated pits to provide the force for pinching the vesicles away from the cell membrane.
Phagocytosis occurs in much the same way as pinocytosis, except that it involves large particles rather than molecules. Only certain cells have the capability of phagocytosis, most notably the tissue macrophages and some of the white blood cells. Phagocytosis is initiated when a particle such as a bacterium, a dead cell, or tissue debris binds with receptors on the surface of the phagocyte. In the case of bacteria, each bacterium usually is already attached to a speciﬁc antibody, and it is the antibody that attaches to the phagocyte receptors, dragging the bacterium along with it. This intermediation of antibodies is called opsonization.
Phagocytosis occurs in the following steps:
1. The cell membrane receptors attach to the surface ligands of the particle.
2. The edges of the membrane around the points of attachment evaginate outward within a fraction of a second to surround the entire particle; then, progressively more and more membrane receptors attach to the particle ligands. All this occurs suddenly in a zipper-like manner to form a closed phagocytic vesicle.
3. Actin and other contractile ﬁbrils in the cytoplasm surround the phagocytic vesicle and contract around its outer edge, pushing the vesicle to the interior.
4. The contractile proteins then pinch the stem of the vesicle so completely that the vesicle separates from the cell membrane, leaving the vesicle in the cell interior in the same way that pinocytotic vesicles are formed.
Digestion of Pinocytotic and Phagocytic Foreign Substances Inside the Cell—Function of the Lysosomes
Almost immediately after a pinocytotic or phagocytic vesicle appears inside a cell, one or more lysosomes become attached to the vesicle and empty their acid hydrolases to the inside of the vesicle. Thus, a digestive vesicle is formed inside the cell cytoplasm in which the vesicular hydrolases begin hydrolyzing the proteins, carbohydrates, lipids, and other substances in the vesicle. The products of digestion are small molecules of amino acids, glucose, phosphates, and so forth that can diffuse through the membrane of the vesicle into the cytoplasm. What is left of the digestive vesicle, called the residual body, represents indigestible substances. In most instances, this is ﬁnally excreted through the cell membrane by a process called exocytosis, which is essentially the opposite of endocytosis. Thus, the pinocytotic and phagocytic vesicles containing lysosomes can be called the digestive organs of the cells.
Regression of Tissues and Autolysis of Cells
Tissues of the body often regress to a smaller size. For instance, this occurs in the uterus after pregnancy, in muscles during long periods of inactivity, and in mammary glands at the end of lactation. Lysosomes are responsible for much of this regression. The mechanism by which lack of activity in a tissue causes the lysosomes to increase their activity is unknown. Another special role of the lysosomes is removal of damaged cells or damaged portions of cells from tissues. Damage to the cell caused by heat, cold, trauma, chemicals, or any other factor induces lysosomes to rupture. The released hydrolases immediately begin to digest the surrounding organic substances. If the damage is slight, only a portion of the cell is removed, followed by repair of the cell. If the damage is severe, the entire cell is digested, a process called autolysis. In this way, the cell is completely removed, and a new cell of the same type ordinarily is formed by mitotic reproduction of an adjacent cell to take the place of the old one. The lysosomes also contain bactericidal agents that can kill phagocytized bacteria before they can cause cellular damage.
These agents include
(1) Lysozyme, which dissolves the bacterial cell membrane;
(2) Lysoferrin, which binds iron and other substances before they can promote bacterial growth; and
(3) Acid at a pH of about 5.0, which activates the hydrolases and inactivates bacterial metabolic systems.
PROCESS OF ENDOCYTOSIS
PROCESS OF PINOCYTOSIS