Membrane Physiology PDF

1A PHYSIOLOGY MEMBRANE PHYSIOLOGY DR. CANCINO, M.D....

1A PHYSIOLOGY MEMBRANE PHYSIOLOGY DR. CANCINO, M.D. than those dominated by saturated FAs because the kinks in the unsaturated FA tails at the locations of the double OUTLINE bonds prevent tight packing. I. Introduction II. Membrane Function III. Membrane Structure IV. Transport Mechanisms across the Membrane II. MEMBRANE FUNCTION A. Passive  Separates cells from outside environment and from each B. Active other C. Bulk Transport  Organizes chemical activities of cell LEGEND: Black – Power point  Controls passage of molecules across membranes Blue – Book  Partitions of organelle function in eukaryotes (e.g. Red – Recorded, Italicized mitochondria has its own membrane)  Regulates the passage of substance into and out of cells I. INTRODUCTION and between cell organelles and cytosol  Detects chemical messengers arriving at the surface A. PLASMA MEMBRANE  Link adjacent cells together by membrane junctions  All cells are surrounded by a plasma membrane.  Anchor cells to the extracellular matrix  Cell membranes are composed of a lipid bilayer with globular proteins embedded in the bilayer. III. MEMBRANE STRUCTURES  On the external surface, carbohydrate groups join with lipids to form glycolipids, and with proteins to form A. PHOSPHOLIPIDS glycoproteins. These function as cell identity markers.  Phospholipids form the basic structure of a cell membrane – lipid bilayer 1. Fluid Mosaic Model  Mainly 2 layers of phospholipids: Non-polar tails that point  1972, S. Singer & G. Nicolson proposed the Fluid Mosaic inward and polar heads that are on the surface Model of the membrane structure. (Dynamic Fluid Mosaic  Contains cholesterol in animal cells Model)  In fluid state, allowing proteins to move around within the bilayer  Cholesterol molecules help to keep the membrane fluid 1.1 Fluidity of Membranes  Most abundant lipid  Membrane molecules are held in place by relatively weak  Polar/hydrophilic head: attracted to water hydrophobic interactions.  Pair of non-polar/hydrophobic tails: repelled by water  Most of the lipids and some proteins drift laterally in the plane of the membrane, but rarely flip-flop from one 1. Phospholipid bilayer phospholipid layer to the other.  Polar heads: outside & inside  Nonpolar tails: interior of cell membranes  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 Trans 1 | Adamag, Alamag, Baltazar, Binwag, Bog-ac 1 of 7  Physiology Membrane Physiology B. MEMBRANE COMPONENTS enzymes in a membrane are organized as a team that carries 1. Steroid Cholesterol out sequential steps of a metabolic pathway.  Wedged between phospholipid molecules in the plasma 3. Cell surface receptor for Signal transduction. A membrane membrane of animal cells protein may have a binding site with a specific shape that fits o  At warm temperatures (37 C), cholesterol restrains the the shape of a chemical messenger, such as a hormone. The movement of phospholipids and reduces fluidity external messenger (signal) may cause a conformational change  At cool temperatures, it maintains fluidity by preventing in the protein (receptor) that relays the message to the inside tight packing of the cell.  Thus, cholesterol acts as a “temperature buffer” for the 4. Cell surface identity marker for Cell-cell recognition. Some membrane, resisting changes in membrane fluidity as glyco-proteins serve as identification tags that are specifically temperature changes. recognized by other cells.  Present in membranes in varying amounts 5. Intercellular joining. Membrane proteins of adjacent cells may  Increases membrane FLEXIBILITY & STABILITY during hook together in various kinds of junctions, such as gap different temperatures junctions or tight junctions  Helps to increase hydrophobicity of membrane 6. Attachment to the cytoskeleton and extracellular matrix 2. Carbohydrates (ECM). Microfilaments or other elements of the cytoskeleton  Interact with the surface molecules of other cells, may be bonded to membrane proteins, a function that helps facilitating cell-cell recognition maintain cell shape and stabilizes the location of certain  Cell-cell recognition is a cell’s ability to distinguish one membrane proteins. Proteins that adhere to the ECM can type of neighbouring cell from another. (Carbohydrates coordinate extracellular and intracellular changes are usually extracellular)  Glycoproteins: majority of integral proteins  Proteoglycans  Glycolipids: approx. 10% o Involved in cell-cell attachments/interactions o Play a role in immune reactions (they serve as a marker for the recognition for immune cells) 3. Proteins  A membrane is a collagen of different proteins embedded in the fluid matrix of the lipid bilayer.  Peripheral proteins – located only on one side; appendages loosely bound to the surface of the membrane either intracellular or extracellular  Integral proteins – embedded/penetrate the hydrophobic core of the lipid bilayer; traverses the lipid bilayer  Many are transmembrane proteins completely spanning the membrane III. TRANSPORT MECHANISM ACROSS MEMBRANE  Provide function to a membrane  Can move laterally  The plasma membrane is the boundary that separates the  Membrane also shows “sidedness” living cell from its non-living surroundings. o Interior: attachment of cytoskeleton, maintains  In order to survive, a cell must exchange materials with its shape surroundings – a process controlled by plasma membrane. o Exterior: carbohydrates, extracellular matrix  Materials must enter and leave the cell through the  Defined by mode of association with the lipid bilayer plasma membrane. o Integral: channels, pores, carriers, enzymes  Membrane structure results in selective permeability; it o Peripheral: enzymes, intracellular signal allows some substances to cross it more easily than others. mediators Note: 3.1 Functions Lipids by themselves are a BARRIER to water & water-soluble 1. Transporter –A protein that spans the membrane may provide substances but it allows lipid-soluble substances to cross the a hydrophilic channel across the membrane that is selective for membrane. a particular solute. 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 A. PASSIVE TRANSPORT 2. Enzyme for Enzymatic activity. A protein built into the  Diffusion of a substance across a membrane with no membrane may be an enzyme with its active site exposed to energy investment. substances in the adjacent solution. In some cases, several  Down a concentration gradient S1T1 2 of 7 Physiology Membrane Physiology  There are 3 special types of diffusion that involve gradient. There will be a net diffusion of the purple molecules movement of materials across a semipermeable towards the left, even though the total solute concentration is membrane. initially greater on the left side. 1.1 Permeability of the Lipid Bilayer  Permeability Factors o Lipid solubility – The higher the lipid solubility, the more permeable (Ex. Oxygen, nitrogen, carbon dioxide, alcohols) o Size – the smaller the size, the more permeable o Charge – presence of charge makes it less permeable o Presence of channels & transporters – aid in the permeability  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. 1. Simple Diffusion  Prerequisite – membrane, solute permeable to the 1.2 Diffusion Rate & Permeability membrane and a concentration gradient a. DIFFUSION – Fick’s First Law  Dialysis/selective diffusion of solutes  Diffusion rate is directly proportional to permeability, o Lipid-soluble materials surface area and concentration gradient of the solute. Thus o Small molecules that can pass through increase in these factors also increases diffusion rate. membrane pores unassisted  Negative – movement is from the outside to inside  The net movement of a substance from an area of higher  Positive – from the inside to the outside concentration to an area of lower concentration  Caused by the constant random motion of all atoms & molecules  Movement of individual atoms & molecules is random, but each substance moves down its own concentration gradient.  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 b. PERMEABILITY continue to cross the membrane, but at equal rates in  Permeability is indirectly proportional to the radius of the both directions. solute, viscosity of the medium and thickness of membrane. Increase in these factors decreases permeability. Two different solutes are separated by a membrane that is permeable to both. Each solute diffuses down its concentration S1T1 3 of 7  Physiology Membrane Physiology SIMPLE DIFFUSION *Additional notes:  No carrier protein required  Osmolality (the Osmole)  Kinetic movement of molecules or ions through a o Unit to express the concentration of a solution in membrane opening or intermolecular spaces terms of the no. of particles  Rate is determined by o Osmolality = ( ) 1. Amount of substance available o The normal osmolality of extracellular and 2. Velocity intracellular fluids is 300 milliosmoles/kg of 3. Number and size of openings in membrane water  Osmolarity 2. Osmosis  Prerequisite – membrane, membrane is permeable to o Osmolarity = ( ) water but not to the solute and a concentration gradient o It is far more practical to measure osmolarity  Simple diffusion of water caused by a concentration than osmolality difference of water 2.2 Tonicity  Diffusion of the solvent/water across a semipermeable  Ability of a solution to cause a cell to gain or lose water – membrane from a region of high concentration to a region bases on the concentration of solutes. where the concentration is lower  Isotonic: ECF and ICF have equal solute concentration  In living systems the solvent is always water, so biologists  Hypertonic: ECF has a higher solute concentration than ICF generally define osmosis as the diffusion of water across a  Hypotonic: ECF has a lower solute concentration than ICF semipermeable membrane from a hypotonic solution to a  Plain Normal Saline Solution - usual isotonic solution. hypertonic solution. Concentration of NaCl in PNSS is equal to the concentration of NaCl inside the RBC 3. Facilitated Diffusion/ Carrier-mediated Diffusion  Specific proteins facilitate diffusion across membranes. o No cellular energy required o Carrier protein interacts with solute  Diffusion of solutes through a semipermeable membrane with the help of special transport proteins i.e. large polar 2. 1 Osmotic Pressure molecules & ions that cannot pass through phospholipid  Osmotic pressure of a solution is the pressure needed to bilayer. keep it in equilibrium with pure water.  Transport proteins can help ions and large polar molecules  The higher the concentration of solutes in a solution, the diffuse through cell membranes by interrupting continuity higher its osmotic pressure. of lipid bilayer. It constitutes an alternate pathway through cell membrane.  Two types: o Channel proteins: provide a narrow channel for the substance (i.e. Water, ions and molecules) to pass through o Carrier proteins: physically bind to the substance on one side of membrane & release it on the other  Still considered a passive transport despite using channel or carrier proteins because it occurs down a concentration a gradient and does not require ATP  Osmotic pressure is directly proportional to the given factors S1T1 4 of 7  Physiology Membrane Physiology PRIMARY SECONDARY Membrane pump Coupled transport Molecules are pumped One molecule down gradient; against concentration One molecule against gradient concentration gradient Gradient at the expense of Driven by the energy stored in energy (ATP) the concentration gradient of  Rate of diffusion is limited by another molecule o Vmax of the carrier protein Direct use of cellular energy Indirect use of energy o Density of carrier proteins (number per unit area) 1. Primary Active Transport Note:  A carrier protein uses energy from ATP to move a Simple diffusion: Increase concentration gradient, increase rate substance across a membrane, up its concentration of diffusion. gradient. Facilitative diffusion: Reaches Vmax; when saturated, it levels  Rate is limited by Vmax off  Up to 90% of cell energy expended for active transport. + +  Na /K ATPase Pump 3.1 Specific o Plays an important role in regulating osmotic  Each channel or carrier transports certain ions or + + balance by maintaining Na and K balance molecules only. o Requires 1-2/3 of cell’s energy o Moves 3 sodium ions outside for every two 3.2 Passive potassium ions inside  Direction of net movement is always down the o They still need carrier proteins. This job can only concentration gradient. be done at a certain rate 2+ +  Others active transport: Ca ATPase, H ATPase 3.3 Saturates  Once all transport proteins are in use, rate of diffusion cannot be increased further. *Additional (Facilitated Diffusion)  Carrier protein binds to molecule and shuttles them through membrane  Vmax – maximum rate of diffusion; limited by the rate at which the carrier protein can undergo conformational changes  Ex. Glucose and amino acid transporters  Factors affecting net rate of diffusion o Concentration difference – net diffusion is from high concentration to low concentration o Electrical potential of ions (Nernst potential) – ex. Even though a concentration gradient doesn’t exist, net diffusion can still occur due to electrical charges (i.e. positive charges attracting 2. Secondary Active Transport negative ions causes movement of ions across  Stages membrane) o Primary Active Transport. Carrier protein uses o Pressure difference – molecules move from high ATP to move a substance across the membrane to low pressure against its concentration gradient. Storing energy. B. ACTIVE TRANSPORT o Facilitated Diffusion. Coupled transport protein  Uses energy (ATP) to move a substance against its natural allows the substance to move down its tendency e.g. up a concentration gradient. concentration gradient using the stored energy  Requires the use of carrier proteins (transport proteins to move a second substance up its concentration that physically bind to the substance being transported). gradient.  Types o Primary (Membrane Pump) o Secondary  Most of active transports are used to create an environment to have other potentials in the membrane S1T1 5 of 7 Physiology Membrane Physiology 2.1 Co-transport  Aka Co-porters  A substance is transported in the same direction as the + driver ion Na  E.g. Amino acids, Glucose, Bicarbonate 2.2 Counter-transport  Aka Anti-porters  A substance is transported in the opposite direction as the + driver ion Na ++ + -  E.g. Ca , H , Cl C. BULK TRANSPORT  Allows small particles, or groups of molecules to enter or leave a cell without actually passing through the membrane.  Mechanisms o Endocytosis o Exocytosis 3. Ion Channels 1. Endocytosis  Voltage gating  The plasma membrane envelops small particles or fluid, o Responds to electrical potential across then seals on itself to form a vesicle or vacuole which membrane + enters the cell: o Ex. Strong negative charge inside cell: Na gates o Phagocytosis - In phagocytosis, a cell engulfs a are closed + particle by wrapping pseudopodia around it and o Ex. Positive charge inside cell: K channels open packaging it within a membrane-enclosed sac  Chemical / ligand gating large enough to be classified as a vacuole. The o Opens when a ligand binds particle is digested after the vacuole fuses with o Ex. Acetylcholine channel – opened by a lysosome containing hydrolytic enzymes acetylcholine (ligand); important for transmission of nerve signals and muscle contractions S1T1 6 of 7 Physiology Membrane Physiology 2. Exocytosis  Reverse of endocytosis  During this process, the membrane of a vesicle fuses with o Pinocytosis - In pinocytosis, the cell “gulps” the plasma membrane & its contents are released outside droplets of extracellular fluid into tiny vesicles. It the cell. 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, pinocytosis is nonspecific in the substances it transports REFERENCES nd 1. Boron WF, Boulpaep EL. Medical Physiology. 2 ed, updated. New York: Saunders-Elsevier, 2012. 2. Hall JE. Guyton and Hall Textbook of Medical Physiology. o Receptor-Mediated Endocytosis - enables the th 13 ed. New York: Saunders-Elsevier, 2016. 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 S1T1 7 of 7