Cell Membrane Structure and Function

1. Cell Membrane Structure and Function

2. Membranes and Cell Transport • All cells are surrounded by a plasma membrane. • Cell membranes are composed of a lipid bilayer with globular proteins embedded in the bilayer. • On the external surface, carbohydrate groups join with lipids to form glycolipids, and with proteins to form glycoproteins. These function as cell identity markers.

3. Fluid Mosaic Model Extracellular fluid Glycoprotein Glycolipid Carbohydrate Cholesterol Transmembrane proteins Peripheral protein Cytoplasm Filaments of cytoskeleton • In 1972, S. Singer and G. Nicolson proposed the Fluid Mosaic Model of membrane structure

4. Phospholipids Choline Hydrophilic head Phosphate Glycerol Hydrophobic tails Fatty acids Hydrophilic head Hydrophobic tails Space-filling model Structural formula Phospholipid symbol • In phospholipids, two of the –OH groups on glycerol are joined to fatty acids. The third –OH joins to a phosphate group which joins, in turn, to another polar group of atoms. • The phosphate and polar groups are hydrophilic (polar head) while the hydrocarbon chains of the 2 fatty acids are hydrophobic (nonpolar tails).

5. Phospholipids • Glycerol • Two fatty acids • Phosphate group Hydrophilic heads ECF WATER Hydrophobic tails ICF WATER

6. Phospholipid Bilayer Polar hydro-philic heads Nonpolar hydro-phobic tails Polar hydro-philic heads • Mainly 2 layers of phospholipids; the non-polar tails point inward and the polar heads are on the surface. • Contains cholesterol in animal cells. • Is fluid, allowing proteins to move around within the bilayer.

7. The Fluidity of Membranes Lateral movement (~107 times per second) Flip-flop (~ once per month) • Membrane molecules are held in place by relatively weak hydrophobic interactions. • Most of the lipids and some proteins drift laterally in the plane of the membrane, but rarely flip-flop from one phospholipid layer to the other. • Membrane fluidity is influenced by temperature. As temperatures cool, membranes switch from a fluid state to a solid state as the phospholipids pack more closely. • Membrane fluidity is also influenced by its components. Membranes rich in unsaturated fatty acids are more fluid that those dominated by saturated fatty acids because the kinks in the unsaturated fatty acid tails at the locations of the double bonds prevent tight packing.

8. Membrane Components Cholesterol • Steroid Cholesterol • Wedged between phospholipid molecules in the plasma membrane of animal cells. • At warm temperatures (such as 37°C), cholesterol restrains the movement of phospholipids and reduces fluidity. • At cool temperatures, it maintains fluidity by preventing tight packing. • Thus, cholesterol acts as a “temperature buffer” for the membrane, resisting changes in membrane fluidity as temperature changes.

9. Membrane Components Fibers of extracellular matrix (ECM) EXTRACELLULAR SIDE Glycoprotein N-terminus Carbohydrate Glycolipid Microfilaments of cytoskeleton C-terminus Peripheral protein Cholesterol Integral protein CYTOPLASMIC SIDE a Helix • Membrane carbohydrates • Interact with the surface molecules of other cells, facilitating cell-cell recognition • Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from another • Membrane Proteins • A membrane is a collage of different proteins embedded in the fluid matrix of the lipid bilayer • Peripheral proteins are appendages loosely bound to the surface of the membrane • Integral proteins penetrate the hydrophobic core of the lipid bilayer • Many are transmembrane proteins, completely spanning the membrane

10. Functions of Cell Membranes • Regulate the passage of substance into and out of cells and between cell organelles and cytosol • Detect chemical messengers arriving at the surface • Link adjacent cells together by membrane junctions • Anchor cells to the extracellular matrix

11. 6 Major Functions Of Membrane Proteins ATP Enzymes Signal Receptor • Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) Other transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as an energy ssource to actively pump substances across the membrane • Enzymatic activity. A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway. • Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell.

12. Glyco- protein 6 Major Functions Of Membrane Proteins 4. Cell-cell recognition. Some glyco-proteins serve as identification tags that are specifically recognized by other cells. 5. Intercellular joining. Membrane proteins of adjacent cells may hook together in various kinds of junctions, such as gap junctions or tight junctions Attachment to the cytoskeleton and extracellular matrix (ECM). Microfilaments or other elements of the cytoskeleton may be bonded to membrane proteins, a function that helps maintain cell shape and stabilizes the location of certain membrane proteins. Proteins that adhere to the ECM can coordinate extracellular and intracellular changes 6.

13. Functions of Plasma Membrane Proteins Outside Plasma membrane Inside Transporter Enzyme Cell surface receptor Cell surface identity marker Attachment to the cytoskeleton Cell adhesion

14. Membrane Transport • The plasma membrane is the boundary that separates the living cell from its nonliving surroundings • In order to survive, A cell must exchange materials with its surroundings, a process controlled by the plasma membrane • Materials must enter and leave the cell through the plasma membrane. • Membrane structure results in selective permeability, it allows some substances to cross it more easily than others

15. Membrane Transport • The plasma membrane exhibits selective permeability - It allows some substances to cross it more easily than others

16. Passive Transport • Passive transport is diffusion of a substance across a membrane with no energy investment • 4 types • Simple diffusion • Dialysis • Osmosis • Facilitated diffusion

17. Kinetic Theory of Matter • All atoms and molecules are in constant random motion. (Energy of motion is called kinetic energy.) • The higher the temperature, the faster the atoms and molecules move. • We detect this motion as heat. • All motion theoretically stops at absolute zero.

18. Solutions and Transport • Solution – homogeneous mixture of two or more components • Solvent – dissolving medium • Solutes – components in smaller quantities within a solution • Intracellular fluid – nucleoplasm and cytosol • Extracellular fluid • Interstitial fluid – fluid on the exterior of the cell within tissues • Plasma – fluid component of blood

19. Diffusion Random movement leads to net movement down a concentration gradient Lump of sugar Water No net movement at equilibrium • The net movement of a substance from an area of higher concentration to an area of lower concentration - down a concentration gradient • Caused by the constant random motion of all atoms and molecules • Movement of individual atoms & molecules is random, but each substance moves down its own concentration gradient.

20. Diffusion Across a Membrane Equilibrium Net diffusion Net diffusion • The membrane has pores large enough for the molecules to pass through. • Random movement of the molecules will cause some to pass through the pores; this will happen more often on the side with more molecules. The dye diffuses from where it is more concentrated to where it is less concentrated • This leads to a dynamic equilibrium: The solute molecules continue to cross the membrane, but at equal rates in both directions.

21. Diffusion Across a Membrane • Two different solutes are separated by a membrane that is permeable to both • Each solute diffuses down its own concentration gradient. • There will be a net diffusion of the purple molecules toward the left, even though the total solute concentration was initially greater on the left side Equilibrium Net diffusion Net diffusion Net diffusion Equilibrium Net diffusion

22. The Permeability of the Lipid Bilayer • Permeability Factors • Lipid solubility • Size • Charge • Presence of channels and transporters • Hydrophobic molecules are lipid soluble and can pass through the membrane rapidly • Polar molecules do not cross the membrane rapidly • Transport proteins allow passage of hydrophilic substances across the membrane

23. Passive Transport Processes • 3 special types of diffusion that involve movement of materials across a semipermeable membrane • Dialysis/selective diffusion of solutes • Lipid-soluble materials • Small molecules that can pass through membrane pores unassisted • Facilitated diffusion - substances require a protein carrier for passive transport • Osmosis – simple diffusion of water

24. Osmosis • Diffusion of the solvent across a semipermeable membrane. • In living systems the solvent is always water, so biologists generally define osmosis as the diffusion of water across a semipermeable membrane:

25. Osmosis Lower concentration of solute (sugar) Higher concentration of sugar Same concentration of sugar Selectively permeable mem- brane: sugar mole- cules cannot pass through pores, but water molecules can Water molecules cluster around sugar molecules More free water molecules (higher concentration) Fewer free water molecules (lower concentration) Osmosis  Water moves from an area of higher free water concentration to an area of lower free water concentration

26. Osmotic Pressure • Osmotic pressure of a solution is the pressure needed to keep it in equilibrium with pure H20. • The higher the concentration of solutes in a solution, the higher its osmotic pressure. • Tonicity is the ability of a solution to cause a cell to gain or lose water – based on the concentration of solutes

27. Tonicity Hypotonic solution Hypertonic solution Isotonic solution H2O H2O H2O H2O Normal Shriveled Lysed • If 2 solutions have equal [solutes], they are called isotonic • If one has a higher [solute], and lower [solvent], is hypertonic • The one with a lower [solute], and higher [solvent], is hypotonic

28. Water Balance In Cells With Walls (b) Plant cell. Plant cells are turgid (firm) and generally healthiest in a hypotonic environ- ment, where the uptake of water is eventually balanced by the elastic wall pushing back on the cell. H2O H2O H2O H2O Turgid (normal) Flaccid Plasmolyzed

29. My definition of Osmosis • Osmosis is the diffusion of water across a semi-permeable membrane from a hypotonic solution to a hypertonic solution

30. Facilitated Diffusion EXTRACELLULAR FLUID Solute Carrier protein Channel protein Solute CYTOPLASM • Diffusion of solutes through a semipermeable membrane with the help of special transport proteins i.e. large polar molecules and ions that cannot pass through phospholipid bilayer. • Two types of transport proteins can help ions and large polar molecules diffuse through cell membranes: • Channel proteins – provide a narrow channel for the substance to pass through. • Carrier proteins – physically bind to the substance on one side of membrane and release it on the other.

31. Facilitated Diffusion • Specific – each channel or carrier transports certain ions or molecules only • Passive – direction of net movement is always down the concentration gradient • Saturates – once all transport proteins are in use, rate of diffusion cannot be increased further

32. Active Transport • Uses energy (from ATP) to move a substance against its natural tendency e.g. up a concentration gradient. • Requires the use of carrier proteins (transport proteins that physically bind to the substance being transported). • 2 types: • Membrane pump (protein-mediated active transport) • Coupled transport (cotransport).

33. Membrane Pump • A carrier protein uses energy from ATP to move a substance across a membrane, up its concentration gradient:

34. The Sodium-potassium Pump • One type of active transport system [Na+] high [K+] low Na+ Na+ 1. Cytoplasmic Na+ binds to the sodium-potassium pump. 2. Na+ binding stimulates phosphorylation by ATP. Na+ Na+ EXTRACELLULAR FLUID Na+ ATP [Na+] low [K+] high P Na+ ADP CYTOPLASM Na+ Na+ 6. K+ is released and Na+ sites are receptive again; the cycle repeats. 3. Phosphorylation causes the protein to change its conformation, expelling Na+ to the outside. Na+ K+ P K+ 5. Loss of the phosphate restores the protein’s original conformation. K+ 4. Extracellular K+ binds to the protein, triggering release of the Phosphate group. K+ K+ K+ P i P P i

35. Coupled transport • 2 stages: • Carrier protein uses ATP to move a substance across the membrane against its concentration gradient. Storing energy. • Coupled transport protein allows the substance to move down its concentration gradient using the stored energy to move a second substance up its concentration gradient:

36. Review: Passive And Active Transport Compared Passive transport. Substances diffuse spontaneously down their concentration gradients, crossing a membrane with no expenditure of energy by the cell. The rate of diffusion can be greatly increased by transport proteins in the membrane. Active transport. Some transport proteins act as pumps, moving substances across a membrane against their concentration gradients. Energy for this work is usually supplied by ATP. ATP Diffusion. Hydrophobic molecules and (at a slow rate) very small uncharged polar molecules can diffuse through the lipid bilayer. Facilitated diffusion. Many hydrophilic substances diffuse through membranes with the assistance of transport proteins, either channel or carrier proteins.

37. Bulk Transport • Allows small particles, or groups of molecules to enter or leave a cell without actually passing through the membrane. • 2 mechanisms of bulk transport: endocytosis and exocytosis.

38. Endocytosis • The plasma membrane envelops small particles or fluid, then seals on itself to form a vesicle or vacuole which enters the cell: • Phagocytosis • Pinocytosis • Receptor-Mediated Endocytosis -

39. Three Types Of Endocytosis PHAGOCYTOSIS In phagocytosis, a cell engulfs a particle by Wrapping pseudopodia around it and packaging it within a membrane- enclosed sac large enough to be classified as a vacuole. The particle is digested after the vacuole fuses with a lysosome containing hydrolytic enzymes. EXTRACELLULAR FLUID 1 µm CYTOPLASM Pseudopodium Pseudopodium of amoeba “Food” or other particle Bacterium Food vacuole Food vacuole An amoeba engulfing a bacterium via phagocytosis (TEM). PINOCYTOSIS In pinocytosis, the cell “gulps” droplets of extracellular fluid into tiny vesicles. It is not the fluid itself that is needed by the cell, but the molecules dissolved in the droplet. Because any and all included solutes are taken into the cell, pinocytosisis nonspecific in the substances it transports. 0.5 µm Plasma membrane Pinocytosis vesicles forming (arrows) in a cell lining a small blood vessel (TEM). Vesicle

40. Process of Phagocytosis

41. Receptor-mediated Endocytosis Coat protein Receptor Coated vesicle Receptor-mediated endocytosis enables the cell to acquire bulk quantities of specific substances, even though those substances may not be very concentrated in the extracellular fluid. Embedded in the membrane are proteins with specific receptor sites exposed to the extracellular fluid. The receptor proteins are usually already clustered in regions of the membrane called coated pits, which are lined on their cytoplasmic side by a fuzzy layer of coat proteins. Extracellular substances (ligands) bind to these receptors. When binding occurs, the coated pit forms a vesicle containing the ligand molecules. Notice that there are relatively more bound molecules (purple) inside the vesicle, other molecules (green) are also present. After this ingested material is liberated from the vesicle, the receptors are recycled to the plasma membrane by the same vesicle. Coated pit Ligand Coat protein A coated pit and a coated vesicle formed during receptor- mediated endocytosis (TEMs). Plasma membrane 0.25 µm

42. Exocytosis • The reverse of endocytosis • During this process, the membrane of a vesicle fuses with the plasma membrane and its contents are released outside the cell: