A closer look at cell membranes Chapter 5 Transport and other things
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Membrane structure and function • LECTURE OBJECTIVES • Describe the structure and dynamic nature of the cell membrane • Demonstrate how extracellular signals generate intracellular events. • Summarize the physical laws and biological processes which govern solute and solvent transport across the cell membrane. • Establish how electrochemical gradients are responsible for establishing a membrane potential.
Cell Membrane • Cell membrane--the barrier between what goes on in the cytoplasm and the cell's immediate environment. • Overall Structure of Cell Membrane • 1. Most of the cell membrane is composed of phospholipids. • The polar ends are lipophobic (=dissolves in lipid with difficulty); the fatty acid tails are lipophilic (=dissolves in lipids easily). • a. Proteins imbedded in the lipid bilayer have many different functions. • 1) Receptors • 2) Ion channels and carrier molecules • 3) Docking proteins • 4) Cell-adhesion molecules (CAMs) • 5) Glycoproteins, glycolipids, etc. • b. Cholesterol
MEMBRANE TRANSPORT Cell membrane is selectively permeable • A. SOLVENT FLOW. • 1. Osmosis is movement of water down its own concentration gradient. • a. Colligative properties • b. Tonicity (Animation) • 2. Filtration - occurs when there is greater hydrostatic pressure on one side of a membrane than on the other • a. Solvent drag • B. SOLUTE FLOW--Physical principles governing movement of solutes. • 1. Diffusion (Example: movement of oxygen from lung to blood) • a. Factors influencing diffusion rate across the cell membrane. • 1) Concentration gradient • 2) Membrane permeability (solute) • 3) Surface area 4) Molecular weight of solute • 5) Membrane thickness
MEMBRANE TRANSPORT Cell membrane is selectively permeable • b. Fick's Law of Diffusion • 1) Importance of diffusion coefficient (e.g. K+ > Na+) 2. Facilitated diffusion (e.g., glucose transport from blood into the cells) • a. Involves a carrier molecule, but solute moves down its conc. gradient • b. Characteristics of carrier-mediated transport • 3. Active Transport • a. Movement of solute against a concentration gradient • b. Carrier-mediated transport • c. Energy (ATP) is expended • 1) Primary Active Transport • a) Structural and biochemical characteristics of the ATPase pump • b) Example: Na+/K+ ATPase pump (Animation) • 2) Secondary Active Transport • a) Co-transport of Na+ and glucose (Animation: Co-transport)
Transport • Passive Transport Processes • a) Diffusion: definition - is the movement of ions or molecules from regions of higher concentration to regions of lower concentration. (Down a concentration gradient)
Facilitated Diffusion • This is similar to simple diffusion in the sense that it is diffusion (across a membrane) from a high concentration to a lower concentration. However, this time the rte of diffusion is greatly accelerated by the action membrane proteins that act as carrier molecules and aid in diffusion. • These "carrier proteins" are known as "Permeases"
Active Transport • These are cell membrane processes that require energy. These processes are also (as far as we can tell) mediated by membrane carrier molecule. (Proteins) • "Active Transport" "pumps" materials across the membrane against the concentration gradient. I.e. from low concentration to high concentration therefore requires energy.
VESICULAR TRANSPORT • Phagocytosisof bacteria, deadcells, etc. • Receptor-mediatedendocytosis and exocytosis
Movement Across Membranes • Simple diffusion: Movement of a solute from an area of high concentration to an area of low concentration. • Facilitative diffusion: Solute combines with a transporter protein in the membrane.
Movement Across Membranes • Osmosis • Movement of water across a selectively permeable membrane from an area of high water concentration to an area of lower water. • Osmotic pressure • The pressure needed to stop the movement of water across the membrane.
Active Transport • Requires energy & membrane proteins • Substance moved AGAINST its concentration gradient
Vesicle Mediated Transport • Vesicles or vacuoles can fuse with the cell membrane
Exocytosis • Exocytosis: Vesicles form inside the cell, move outward, fuse with the cell membrane, and expel their contents.
Endocytosis: Three Types • Phagocytosis (cell eating): a solid substance brought into the cell • What organelle will fuse with the vesicle once inside the cell? • Pinocytosis (cell drinking): substance is a fluid • Receptor-Mediated: molecule attaches to a specific receptor on the cell surface before a vesicle forms around the molecule
Receptor-Mediated Endocytosis • Note the receptors and path of the LDL • Correlate this slide with the information in your book.
Plasma Membrane - review • Phospholipidbilayer • Peripheral proteins • Integral proteins • Transmembrane proteins • Sterols • Glycocalyx carbohydrates
Plasma Membrane - review • Selective permeability allows passage of some molecules • Simple diffusion • Facilitative diffusion • Osmosis • Active transport • Endocytosis • Phagocytosis: Pseudopods extend and engulf particles • Pinocytosis: Membrane folds inward bringing in fluid and dissolved substances
Testing your knowledge Questions to answer in the process
Questions… • Describe the fluid mosaic model of membrane structure. What are the functions of the major components? Which components do not move easily? Why don't they? • Give at least four different functions for the proteins that are embedded in the cell membrane. • What is Fick's law of diffusion? What factors influence the rate of diffusion across a membrane? Give examples of how membranes might be altered in a biological system to change the rate of diffusion. Can you give a few examples of where diffusion is important for proper physiological function • What are desmosomes, tight junctions, and gap junctions? Under which circumstances is each important? • Compare and contrast the major avenues of water transport across the cell membrane. Give an example of where each is important in human physiology. How are solutes transported across the cell membrane? Compare and contrast the functional characteristics of each transport mechanism. Give an example of how each is important in human physiology.
Questions… • Give at least four different functions for the proteins that are embedded in the cell membrane.
REASONING AND PROBLEM SOLVING • Because of its charge, glucose normally diffuses through the cell membrane very slowly. However, facilitated diffusion of glucose occurs more rapidly as long as the carrier molecules are not saturated. Given Fick's Law of Diffusion, which parameter(s) must change to permit this more rapid diffusion in the presence of a carrier. Explain. • What are the possibilities for how drugs might act at the level of the receptor? In class, I said that a drug could act by competitive inhibition. But some drugs act on the receptor by allosteric (=noncompetitive) inhibition. How might a drug inhibit a receptor in an allosteric manner? • In carrier-mediated transport of Solute Q, there is always the possibility that a similarly-shaped molecule might compete for the transport protein (that is, act as a competitive antagonist to transport of the Solute Q). Graph the rate of Solute Q transport (Y axis) against increasing Solute Q concentration (X axis) in the 1) presence and 2) absence of a set amount of competitive antagonist. Explain. Would you expect to find a similar effect in other systems which employ this "lock and key" interaction (e.g., between a substrate and its enzyme or a neurotransmitter and its receptor)? Explain.
Review and Cell Membrane Proteins Looking at what we saw and adding some new stuff
Function of Cholesterol • Provide structural support, prevent small molecule to pass • Prevent tight packing and transition
Microdomains on plasma membrane Lipid rafts (~ 50nm) Choresterol Sphingolipids (long saturated chains) Other proteins
Phospholipids in cell signaling PKC Calcium GEF, AKT, migrating front
Summary Lipid molecules: phospholipids, cholesterol, glycolipid, all amphipathic Lipid bilayer, hydrophobic inside and hydrophilic outside Subdomains on membrane, asymmetry important for functions Phospholipids as signals
Membrane Proteins Integral membrane protein Peripheral membrane protein Glycosylphosphatidylinositol (GPI) anchor protein
Fatty acid chain (acyl, N-terminal) or prenyl group modifications (C-terminal)
Membrane proteins are glycosylated Sugar are added in the lumen of the ER and Golgi apparatus, therefore, sugar are outside of cell surface Cytosol has reduced environment, preventing disulfide bonds
Proteins restrictions Tight Junction is one kind of them Proteins and lipids on the outer layers can’t move to other compartments
Types of Transport Proteins • Uniport carries a single molecule across a membrane • Ex: Glucose enters a cell • Symport moves two different molecules at the same time in the same direction. Both must bind to protein • Ex: Na+ and Glucose enter a cell • Antiport two molecules move in opposite directions • Ex: Na+ and K+ move through a membrane • These proteins can be inhibited by molecules that mimic the normally transported molecules.
Test your knowledge • 1) What is a cell membrane? • 2) What are some functions of the cell membrane? • 3) Does water cross the cell membrane? How? • 4) What determines the flow of water through the membrane? What does diffusion mean? How does it work? • 5) Will the final concentration of water in and out of the cell the same or different? • 6) Does everything cross the cell membrane? • 7) What would happen to a cell if the concentration of water in the cell was less then the concentration of water outside the cell? • 8) What would happen to a cell if the concentration of water in the cell was greater then the concentration of water outside the cell?
Answers • 1) It is the outer layer of the cell much like the cell’s skin. It holds the cell together and regulates what can flow into and out of the cell. • 2) Holds cell together. Let’s some things through and keeps others out. • 3) Yes. It flows through pores in the cell membrane. • 4) Water can flow through the cell membrane’s pores. Water will flow until the concentration of the water in and out the cell is in equilibrium. • 5) It will be the same because water will flow through the membrane until equilibrium is reached. • 6) No, some molecules will not fit through the pores in the cell membrane. • 7) Water would flow into the cell. The cell would grow and / or burst. • 8) Water would flow out of the cell. The cell will shrink.
Laboratory Looking at how the cell work live!!!! CellMembranes and DiffusionLab