Dept.Anat. cytology/lec3 Dr.sarab Eukaryotic cell Structural organization: Although the cells are variable in their shapes, sizes and functions, they are well organized structures and usually contain the same components . The cellular protoplasm is formed of two parts: 1. Cell cytoplasm 2. Nucleoplasm Plasma membrane: Biological membranes include all intracellular membranes and plasma membrane . Generally, these intracellular membranes perform the following important functions: 1- Separate the cell from the outside environment (they act as barrier to isolate the cell from other environmental components). 2- Regulate the passage of materials and exchange of molecules between the cell and outside environment. 3- Participate in many chemical reactions. They contain enzymes and other molecules that are necessary for chemical changes. 4- Transmit signals and information from out-side to inside the cell in a process called cell transduction. 5- Transfer and store energy (ATP). Structure of Biological Membranes All biological membranes including plasma membrane and intracellular membranes have a general structure. The cellular membranes are structurally similar except that the cell membrane of cell surfaces is characterized by occurrence of 1 receptors for cell signals, protein molecules for intercellular communication and immunological differentiation. The most widely accepted model of plasma membrane structure is the fluid mosaic model of Singer & Nicolson (1972). According to this model the cell membrane is composed of a fluid lipidbilayer with a constantly changing mosaic pattern of associated proteins . The molecular composition of cell membrane includes mainly 3 components: a. Lipid bilayer b. Membrane protein c. Membrane carbohydrate. Membrane Lipid Bilayer It is formed of two leaflets. They are composed of: 1. Phospholipid molecules. They form the most forming molecules. 2 2. Glycolipid. It is formed of a carbohydrate chain attaching the hydrophilic glycerol. 3. Cholesterol. 3 The phospholipid molecules and all lipid molecules that make the core of cell membrane are amphipathic molecules. They composed of: a. Hydrophilic (water-loving) polar head group directed toward outside, and b. Hydrophobic (water-hating) non-polar tails of fatty acid chains (one usually unsaturated) and directed toward inside. At body temperature the lipid bilayer is fluid and allows for the lipid molecules to move along the monolayer, reseals spontaneously at injury, and below 17 ᵒC the lipid becomes viscous or crystal-line in nature. The general characteristics of the lipid bilayer can be summarized as follows: 1. Acts as a barrier between two liquid (intra-cellular and extracellular) compartments. 2. Lipid bilayer behaves as a liquid crystals, because of the ordered array of molecules (heads on the outside and the tails of fatty acid chains are directed toward inside). 3. The hydrocarbon chains are in constant motion forming fluid of lipid molecules. The molecules are free to rotate. Each molecule can move laterally within its single layer depended on two factors: 1-temperture and 2- lipid composition(such as shorter fatty acids are weaker and less rigid .Unsaturated fatty acid similarly increase membrane fluidity because the presence of double bonds . 4 4. At body temperature and generally over 25 ᵒ C lipid bilayer is thin fluid layer of about 3.9 nm thickness but it becomes thick viscous layer of about 4.8 nm in thickness under 17ᵒc. 5. Resists forming free ends. It is self sealing and rounds up to form closed vesicles as in formation of transport vesicles and secretory vesicles . 6. Fuses with lipid bilayer of other membranes as in exocytosis. 7. Flexible. It allows change shape without breaking. 8. Cholesterol molecules are largely hydrophobic molecules that maintain the optimal fluidity of lipid bilayer. Cholesterol plays an important role in maintaining of the stability of cell membrane. a. In high temperature; increase the body temperature that increases the movement of membrane molecules, it restricts the movement of molecules and prevents weakening of membrane. b. In low temperature, it restricts solidification (act as spacer). Permeability of lipid bilayer Lipid bilayer is freely permeable for: 1. Gases such as nitrogen, oxygen and carbon dioxide. 2. Hydrophobic hydrocarbon or fat soluble compounds such as steroid hormones. 3. Small polar molecules such as water, glycerol and urea. 5 Lipid bilayer is not permeable for: 1. Large polar molecules such as glucose (mono-saccharide) and disaccharides. 2. Charged molecules such as ions of sodium, potassium, calcium, hydrogen and magnesium and amino acids or polypeptide molecules. Membrane Proteins According to the fluid mosaic model, a cellular membrane consists of a fluid bilayer of lipid molecules in which the proteins are embedded or associated much like the tiles in a mosaic picture. Types of Membrane Proteins: proteins are the major constituent of cell membrane ,(25 to 75)% of the mass of the various membranes of the cell. Morphologically membrane proteins are classified into: 6 a. Integral membrane proteins (firmly bound). They are amphipathic molecules with hydrophobic and hydrophilic regions. They are partially embedded in lipid bilayer or formed of transmembrane proteins .They are exposed on both sides of the membrane. b. Peripheral proteins (loosely associated). They are located on inner or outer surfaces of lipid bilayer and attached to hydrophilic part of integral membrane proteins or the phospholipid molecules. Distribution of membrane protein in lipid bilayer is asymmetrically oriented. The majority of protein molecules attach to the protoplasmic layer of lipid bilayer (inner layer). According to the functions, membrane proteins can be classified into: 1. Cell – cell adhesion proteins. 2. Cell – Extracellular matrix adhesion proteins. Integrins are example for membrane proteins that connect between extracellular matrix and the cytoskeleton. 3. Membrane transport protein. They work to transport specific molecules across the cell membrane. a. Channel proteins for passage of ions or specific molecules. b. Pumps or carrier proteins for active or mediated passive transport. 7 4. Membrane –bound enzymes are important to catalyze chemical reactions. 5. Receptor proteins for recognition and defense. 6. Signal receptor proteins for signal transduction to interior of the cell. Membrane Carbohydrate (cell coat or glycocalyx) Membrane carbohydrates are sugar residues attaching the membrane proteins to form the cell coat or glycocalyx on the external cell surface. There are three forms of membrane carbohydrates: 1. Glycoproteins. They are oligo or polysaccaharide chains attached to membrane proteins. 2. Glycolipids. They are oligosaccharide chains attached to lipid monolayer. 3. Proteoglycans. They are formed of a core of protein surrounded by long polysaccharide chains across the lipid bilayer. *Membrane carbohydrates have the following functions: a. Fill the spaces between the adjacent cells .The cell coat help in holding adjacent cells together. b. Intercellular communication (cell contact).By recognition of chemical message by the cell surface receptors which can receive chemical message and neurotransmitter signal from other cells. c. Cell recognition process .The cell coat enable cells to recognize cells of their own special kind .This is important in transplantation of kidney, heart and skin. d. Mechanical strength of multicellular tissue and organs. 8 f. formation of cell immunity :the cell coat plays an important role in the development of cell immunity against infections. e- production of cell Allergy : The cell coat reacts with foreign materials producing surface cell reaction which protect the body against certain harmful agents. Ways of Transport of Molecules across the Cell Membranes 1. Transport of small molecules: There are two mechanisms for transport of small molecules: a. Passive diffusion b. Active transport. The followings are ways of transporting small molecules across the cell membrane: 9 A) Transport of Small Molecules 1-Passive Transport of Small Molecules a. Simple passive diffusion It is defined as a physical random motion of particles from higher to lower concentration gradient. This motion of particles in passive diffusion continues till equilibrium is reached. The rate of diffusion of molecules across the biological membranes depends upon: - Size of molecules. The smaller molecules diffuse rapidly than the larger ones - Shape of molecules increases or decreases the rate of transport of molecules. Electrical charge. Charged molecules can-not diffuse through the biological membrane, while small polar molecules are freely diffuse. - Temperature. The rate of diffusion of small molecules increases with increase of temperature. - Dialysis and osmosis are examples for simple passive diffusion. Water, gasses and glycerol are examples for molecules that can transport passively from higher concentration to lower concentration. b. Facilitated passive diffusion It is a transport process in which the passage of specific molecules from higher to lower concentration gradient is mediated by Carrier and Channel proteins. Examples: Amino acids, organic acids and inorganic salts. 11 2-Active Transport of Small Molecules It is the process of pumping of molecules or ions through the cell membrane against their concentration gradient. This process requires: a. Transporter (carrier transport protein) b. Energy Types of active transport: a. Direct active transport. It uses ATP hydrolysis to carry out transport of specific molecules against their concentration gradient. b. Indirect active transport (co-transport). It is a process in which directly pumped molecule transport another specific molecule indirectly. Membrane Transport Proteins There are two types of transport proteins: A. Channel Proteins B. Carrier proteins Dialysis It is the process of diffusion of a solute (dissolved substances) across a selectively permeable membrane (such as hemodialysis and peritoneal dialysis). It is used for separation of substances in solution by means of their unequal diffusion through semipermeable membrane . 11 Hemodialysis; dialysis of the blood is used to remove toxic substance or metabolic wastes from blood stream in case of kidney failure. Osmosis It is the diffusion of solvent (water molecules) through a semipermeable membrane from a higher concentration to a lower concentration until the concentration on both sides of the semipermeable membrane becomes equal . The force that must be applied to prevent the motion across the semipermeable membrane is called the osmotic pressure of solution. Notice: Solvent is a substance that is capable of dissolving another substance (solute). 12 B) Ways of Transport of Macromolecules 1. Endocytosis It is a process of internalization of macromolecules from outside into inside the cell. This process is classified into phagocytosis and pinocytosis according to the nature of the internalized materials . Engulfing or eating large foreign solid particles such as bacteria is called phagocytosis, while the process of cellular drinking of fluid containing soluble particles is called pinocytosis. 13 2. Exocytosis It is the reverse process of endocytosis; it means transport of a processed or synthesized cellular product from inside to outside the cell . Mechanism of exocytosis 1. Exocytosis starts by fusion of secretory vesicle membrane with the plasma membrane. 2. An opening is formed between the lumen of secretory vesicle and outside the cell. 3. The contents are released through the opening. Receptor-mediated endocytosis: — It is form of pinocytosis that is specific because it involves the use of a receptor protein shaped in such a way that a specific substance such as vitaminms , hormones can bind to it. 14