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PLASMA MEMBRANE: STRUCTURE AND FUNCTION SHERWOOD: Chapters 3 & 4  FUNCTIONS OF CELL MEMBRANE Homeostasis & cell survival: maintain intracellular contents of cells & coordinate activity with others – Mechanical barrier – Adhere together to form tissues – Exchange nutrients, was...

PLASMA MEMBRANE: STRUCTURE AND FUNCTION SHERWOOD: Chapters 3 & 4  FUNCTIONS OF CELL MEMBRANE Homeostasis & cell survival: maintain intracellular contents of cells & coordinate activity with others – Mechanical barrier – Adhere together to form tissues – Exchange nutrients, wastes & secretions – Respond to changes in environment or signals – Maintain ionic gradient for electrical activity  Sherwood, Fig 3-2 COMPONENTS OF CELL MEMBRANE Lipids: phospholipids and cholesterol – Barrier to passage of water-soluble substances – Provides fluidity & stability to the membrane  Siefter, Fig 2-3 & 2-4 COMPONENTS OF CELL MEMBRANE Proteins: transmembrane or one surface only I III II COMPONENTS OF CELL MEMBRANE Proteins: several types for specific functions – Aquapoins: – Ion channels: – Carrier molecules: – Membrane receptors: – Docking-marker acceptors: – Membrane-bound enzymes: – Cell adhesion molecules (CAMs):  Sherwood , Fig 3-3 COMPONENTS OF CELL MEMBRANE Carbohydrates: present on outer surface only – Glycolipids: Glycocalyx – Glycoproteins: – Function: self-identity markers  Sherwood, Fig 3-1, Fig 3-3 STRUCTURE OF CELL MEMBRANE The fluid mosaic model: Tri-laminar structure  Sherwood, Fig 3-3 STRUCTURE OF CELL MEMBRANE The fluid mosaic model: Tri-laminar structure  CELL-CELL ADHESIONS Cells Tissues Organs System Organism Extracellular matrix (biological glue secreted by cells) Specialized cell junctions: – Desmosomes – Tight junctions – Gap junctions Cell adhesion molecules: – Occurs between cells in close proximity – Loop and hook shaped proteins that “velcro” together  EXTRACELLULAR MATRIX AKA Interstitial fluid, present in intercellular space Meshwork of fibrous proteins in a watery gel – Collagen: – Elastin: – Fibronectin:  EXTRACELLULAR MATRIX Secreted by cells, important for their functioning Pathway for diffusion of water-soluble substances Regulates behavior and functions of the cells: – Amount & composition of ECM varies with cell type Can become highly specialized for specific functions: – Examples: cartilage, tendons, hardness of bones & teeth etc.  Sherwood, Fig 3-4 DESMOSOMES/ADHERING JUNCTIONS “Spot rivets” Plaque Glycoprotein filaments Keratin filaments Present in skin, heart, uterus etc.  Sherwood, Fig 3-5 TIGHT/IMPERMEABLE JUNCTIONS Cells adhere firmly, seals formed at kiss sites by junctional proteins Found b/w epithelial cells, separate 2 compartments of diverse chemical compositions e.g., intestines, kidneys Passage of materials takes place through cells, not between cells, via channels and carriers  Sherwood, Fig 3-6 GAP/COMMUNICATING JUNCTIONS Gaps/tunnels between cells Connexons: six subunits in a hollow tube-like structure, 2 connexons join together Only small particles pass Present in electrically active cardiac/smooth muscle Enables synchronized action Metabolic/communication link  MEMBRANE TRANSPORT Essential for homeostasis: nutrients in, wastes out Plasma membrane is selectively permeable Factors affecting membrane permeability: – Lipid solubility: – Particle size: Forces are required for membrane transport – Passive force: no energy expenditure by cells for transport – Active force: energy (ATP) expenditure by cells for transport  MEMBRANE TRANSPORT Unassisted Assisted Diffusion Osmosis Vesicular transport Carrier mediated Movement along electrical gradient Endocytosis Exocytosis Facilitated diffusion Active transport Primary Active transport Secondary Active transport Caveolae: membrane transport and signal transduction  Sherwood, Fig 3-7 DIFFUSION  Sherwood, Fig 3-8 DIFFUSION  Sherwood, Table 3-1 DIFFUSION Rules/Properties: – Occurs only if substances can cross the membrane – Always occurs from area of high to low concentration – No energy required, a passive mechanism, e.g.O2-CO2 Factors influencing rate of diffusion (Fick’s law):  Sherwood, Fig 3-13 ELECTRICAL GRADIENT EG: charge difference between adjacent areas Promotes movement towards opposite charge Electrical and concentration gradient = electrochemical gradient Positively Negatively charged area charged area Cations (positively charged ions) attracted toward negative area Anions (negatively charged ions) attracted toward positive area  Sherwood, Fig 3-9 & 3-15 OSMOSIS Net diffusion of water down its own concentration gradient separated by semi-permeable membrane Membrane H2 O Higher H2O Lower H2O concentration, concentration, lower solute higher solute concentration concentration  Sherwood, Fig 3-16, 3-17 & 3-18 OSMOSIS Membrane (permeable to Membrane (permeable to H2O Membrane (permeable to H2O both water and solute) but impermeable to solute) but impermeable to solute) H2 O H2 O H2 O Solute Original Original Osmosis Hydrostatic level of level of (fluid) solutions solutions Hydrostatic pressure pressure difference Water concentrations equal Water concentrations equal Water concentration not equal Solute concentrations equal Solute concentrations equal Solute concentration not equal No further net diffusion No further net diffusion Osmosis ceases when osmotic Steady state exists Steady state exists pressure is exactly balanced by opposing hydrostatic pressure  Sherwood, Fig 3-13 OSMOSIS Important for water movement of in/out of cells – Intravenous administration, eye drops etc. Tonicity: conc. of non-penetrating solutes Osmolarity: concentration of non-penetrating and penetrating solutes 300mOsm 0.9% NaCl  CARRIER-MEDIATED TRANSPORT Utilize carriers: membrane spanning proteins Able to flip-flop, a reversible change in shape Binding sites of substance on carriers exposed alternatively to either side of the membrane Conformation X of carrier Conformation Y of carrier On binding with molecules to be transported, carrier changes its conformation  Seifter, Fig 2-11 CARRIER-MEDIATED TRANSPORT  CARRIER-MEDIATED TRANSPORT Specificity and selectivity: – One carrier for one (or closely related) substance – Different cells may have different carriers – Dysfunction leads to diseases Saturation: – Finite number of carriers, affinity/number can be regulated – Tm = transport maximum (rate-limiting factor in transport) Competition: – Occurs when carrier transfers closely related substances – Reduces the rate of transfer of each substance transported – Does not affect the total amount of transfer  Sherwood, Fig 3-14 FACILITATED DIFFUSION  Sherwood, Fig 3-15 FACILITATED DIFFUSION Example: transport of glucose into the cell Movement of a substance from high to low concentration Does not require energy  ACTIVE TRANSPORT Movement of a substance from low to high concentration – Example: uptake of iodine in thyroid gland cells Two types: – Primary active transport: ATP required directly; carrier splits ATP (has ATPase activity) Requires energy (ATP) to change the shape of the carrier AKA “pumps” (hydrogen ion pump, Na-K-ATPase pump) – Secondary active transport: ATP not required directly; carrier lacks ATPase activity  Sherwood, Fig 3-16 PRIMARY ACTIVE TRANSPORT  Na+ K+ ATPase PUMP Establishes Na+ and K+ concentration gradients: electrical signals Regulates cell volume by controlling tonicity Energy (ATP) used also serves for secondary active transport http://blogs.scientificamerican.com/urban- scientist/hotline-bling-sodium-potassium- pumps/ Movie to summarize  Sherwood, Fig 3-18 SECONDARY ACTIVE TRANSPORT  Sherwood, Fig 3-18 SECONDARY ACTIVE TRANSPORT  SECONDARY ACTIVE TRANSPORT Co-transport of glucose and amino acids Intestinal and kidney cells, against concentration gradients Energy not expended directly, mediated by co- transport carriers Contain two binding sites, one for Na other for nutrient molecule Na binding  affinity for glucose binding Transported out in blood by facilitated diffusion  VESICULAR TRANSPORT Large polar molecules (hormones) and multi- molecular materials (bacteria) Wrapped-up in a membrane-enclosed vesicle Requires energy Materials inside do not mix with cytosol, fuse with target membrane for transfer Two types: endocytosis and exocytosis  VESICULAR TRANSPORT Endocytosis: substances transported into the cell, can fuse with lysosome or released on the other side of cell – Pinocytosis (non-selective uptake of ECF) – Receptor-mediated endocytosis (selective uptake of large molecule) – Phagocytosis (selective uptake of multimolecular particle) Exocytosis: substances transported out of the cell, accomplishes two major purposes – Provides a mechanism for secreting hormones/enzymes (large polar molecules) – Enables cell to add specific membrane components: carriers, channels, receptors Rate of endocytosis = rate of exocytosis  Sherwood Fig 2-6 VESICULAR TRANSPORT  Sherwood Fig 2-9 TYPES OF ENDOCYTOSIS (c) Phagocytosis  Seifter, Fig 3-1 CELL-CELL COMMUNICATION Co-ordination of activity & homeostasis Achieved by: – Direct communication: Gap junctions Tunneling nanotubes Juxtacrine – Indirect communication: Paracrine Autocrine Via chemical Endocrine messengers Neuronal  Sherwood, Fig 4-19 COMMUNICATION VIA GAP JXNS Most intimate & rapid means of communication  Sherwood, Fig 4-19 JUXTACRINE COMMUNICATION Direct contact through plasma membranes Restricted to cells in contact (cannot diffuse) Ag-Ab reaction, phagocytosis, CAMs etc.  Sherwood, Fig 4-19 AUTO/PARACRINE COMMUNICATION Autocrine: Paracrine:  Sherwood, Fig 4-19 ENDOCRINE COMMUNICATION Hormones secreted in blood Travel to distant sites Acts on cells possessing receptors FSH, thyroid, insulin etc.  Sherwood, Fig 4-19 NEURONAL COMMUNICATION Short range, released by electrical signals Diffuse to act on target cells (gland/neuron/muscle) Local Neurotransmitter target cell  SIGNAL TRANSDUCTION Chemical messengers: lipid soluble or water soluble Signal transduction process: → message (signal) is “transduced” inside the cell by “transducers” (convert one form of energy to another e.g., radio/phone) Lipid soluble: cross membranes → affect gene transcription → affect activity of proteins Water soluble: do not cross membranes, bind to receptors → transduce signal inside the cell – 1st Messenger-receptor binding → intracellular events: By opening/closing ion channels allowing ions to move in/out By transferring the signal to intracellular 2nd messenger  Sherwood, Table 4-3, Fig 4-28 SIGNAL TRANSDUCTION  ION CHANNELS Leak channels Gated channels Always open, permit leakage Open/close in of ions into/out of cells response to stimuli Ligand-gated Voltage-gated ion channels ion channels Chemical messenger binds Changes in electrical to a receptor associated status of the plasma with ion channel membrane Ionic movement leads to physiological response  Sherwood, Fig 4-21, 4-25, 4-26 SECOND MESSENGER PATHWAYS  Sherwood, Fig 4-27 SECOND MESSENGER PATHWAYS Message is “relayed” inside the cell via 2nd messenger 2nd messengers relays it further to other IC proteins Signaling cascade amplifies the initial response Major ones: – Cyclic AMP – Ca2+/DAG Others exist! Disturbances lead to diseases  Sherwood, Fig 3-19 MEMBRANE POTENTIAL PM is polarized electrically = membrane potential – Separation of opposite charges across the membrane due to difference in relative number of cations/anions  MEMBRANE POTENTIAL “Potential” (capacity) to do work – Unlike charges attract, energy used to separate them – When allowed to come together, energy released – This energy is harnessed to perform work Membrane itself is not charged! Measured in millivolts (one-thousandth of a volt) – Depends on the “degree” of separation  Sherwood, Table 3-3 GENERATION OF RMP Constant membrane potential of tissues at rest: −70mV Unequal distribution of Na+, K+ & A- across membrane – Na-K-ATPase pump Pumps three Na+ outside and two K+ inside Outside becomes more positive than inside, membrane potential! – Leak channels for Na & K ions Always open, allow passive diffusion due to concentration gradient Ion Extracellular Intracellular Relative concentration concentration permeability Na+ 150 mM 15 mM 1 K+ 5 mM 150 mM 25-30 A- 0 mM 65 0  Sherwood, Fig 3-20 GENERATION OF RMP Equilibrium potential of K+ (EK+): Concentration gradient = electrical gradient Given by Nernst equation: E = 61 log Co/Ci EK+ = 61 log 5/150 EK+ = 61 (-1.477) EK+ = -90mV  Sherwood, Fig 3-21 GENERATION OF RMP Equilibrium potential of Na+ (ENa+): – Concentration gradient for Na+ pushes it in leaving Cl- outside – Concentration gradient = electrical gradient – Given by Nernst equation: E = 61 log Co/Ci ENa+ = 61 log ____/___ ENa+ = 61 (_______) ENa+ = _____mV – ENa+ lower than EK+: why?  Sherwood, Fig 3-22 GENERATION OF RMP Concurrent effect of Na+ & K+ movement: movie  Sherwood, Fig 4-1 CHANGES IN RMP Polarization: any state, positive or negative, other than 0 mV  MEMBRANE POTENTIAL: USE Nerve & muscle cells are excitable tissues Undergo transient, rapid changes in their RMP Triggering event Membrane permeability changes Membrane potential changes Ions move across cell membranes Electrical signals Graded potentials: Initiate contraction Travel short distances Types Functions Action potentials: Receive,process, initiate Travel long distances & transmit messages