Membrane Transport• Plasma membrane is selectively permeable – Impermeable membrane - membrane though which nothing can pass – Freely permeable membrane - any substance can pass through it – Selectively permeable membrane - permits free passage of some materials and restricts passage of others • Distinction may be based on size, electrical charge, molecular shape, lipid solubility• Cells differ in their permeabilities; depending on – what lipids and proteins are present in the membrane and – how these components are arranged.
Membrane Permeability• Passage across the membrane is either passive or active – Passive transport requires no ATP • movement down concentration gradient • filtration and simple diffusion –Active transport requires ATP • movement against concentration gradient • carrier mediated • vesicular transport
Types of Transport Processes• Diffusion – results from random motion of particles (ions, molec.) – is a passive process• Carrier-mediated transport – Requires the presence of specialized integral proteins – Can be passive or active• Vesicular transport – Movment of materials with small membranous sacs, or vesicles – Always an active process
Membrane Permeability• Diffusion through lipid bilayer – Nonpolar, hydrophobic substances diffuse through lipid layer; these are “lipid soluble” or lipophilic (fat-loving) substances• Diffusion through channel proteins – water and charged hydrophilic solutes diffuse through channel proteins; these are lipid insoluble or lipophobic (fat fearing) substances• Cells control permeability by regulating number of channel proteins
Simple Diffusion• Net movement of particles from area of high concentration to area of low concentration – due to their constant, random motion – Difference between the high and low concentrations is a concentration gradient – Diffusion tends to eliminate the gradient – Also known as movement “down the concentra- tion gradient”
Diffusion• Examples: – Scent of fresh flowers, drop of ink coloring a glass of water, movement of oxygen and CO2 through cell membranes• Simple diffusion – nonpolar and lipid- soluble substances – Diffuse directly through the lipid bilayer – Diffuse through channel proteins
Factors that Influence Diffusion Rates • Distance - – The shorter the distance, the more quickly [ ] gradients are eliminated – Few cells are father than 125 microns from a blood vessel • Molecular Size – Ions and small molecules diffuse more rapidly • Temperature - ↑ temp., ↑ motion of particles • Steepness of concentrated gradient - – The larger the [ ] gradient, the faster diffusion proceeds • Membrane surface area - – The larger the area, the faster diffusion proceed
Diffusion Across Membranes• Simple Diffusion – Lipophilic substances can enter cells easily because they diffuse through the lipid portion of the membrane • Examples are fatty acids, steroids, alcohol, oxygen, carbon dioxide, and urea,• Channel-Mediated Diffusion – Membrane channels are transmembrane proteins • Only 0.8 nm in diameter – Used by ions, very small water-soluble compounds – Much more complex than simple diffusion • Are there enough channels available? • Size and charge of the ion affects which channels it can pass through
Diffusion Through the Plasma Membrane Figure 3.7
Effect of Membrane Permeability on Diffusion Figure 3.8a
Osmosis: A Special Case of Diffusion• Each solute in the intra- and extracellular fluids diffuses as if it were the only material in solution. – From more to less, i.e., down the [ ] gradient – Some into the cytosol, others out of the cytosol – Yet, total concentration of ions and molecules on either side of the membrane stays the same – This equilibrium persists because a typical cell membrane is freely permeable to water.• Whenever a solute concentration gradient exist, a concentration gradient for water also exists. – Thus, the higher the solute concentration, the lower the water concentration.
Osmosis - By Definition• Movement of water• Across a selectively permeable membrane• Down its concentration gradient (from high to low concentration)• Toward the solution containing the higher solute concentration – This solution has a lower water concentration – Continues until water concentrations and solute concen- trations are the same on either side of the membrane
Effect of Membrane Permeability on Diffusion and Osmosis Figure 3.8b
Osmolarity and Tonicity• Mole - the gram molecular weight of a substance – 1 mole of Glucose =180; 1 mole of NaCl = 58.5• Molarity - the number of moles of solute per liter of solution – 1.0 M glucose contains 180 g/L; 1.0 M NaCl contains 58.5 g/L – Most body fluids are less concentrated than 1 M; use mM (millimolar) or µM (micromolar) concentrations --10-3 and 10-6, respectively.• Osmolarity = the total solute concentration in an aqueous solution – Osmolarity = molarity (mol/L) x # of particles in solutions • A 1 M Glucose solution = 1 Osmolar (Osm) • But a 1 M NaCl soln = 2 Osmolar because NaCl dissociates into 2 particles (Na and Cl) whereas Glucose does not • A 1 M MgCl2 solution = what osmolarity???? __________• Physiological solutions are expressed in milliosmoles per liter (mOsm/L) – blood plasma = 300 mOsm/L or 0.3 Osm/L
Tonicity• Tonicity - ability of a solution to affect fluid volume and pressure within a cell – depends on concentration and permeability of solute• Isotonic solution – solution with the same solute concentration as that of the cytosol; normal saline• Hypotonic solution – lower concentration of nonpermeating solutes than that of the cytosol (high water concentration) – cells absorb water, swell and may burst (lyse)• Hypertonic solution – has higher concentration of nonpermeating solutes than that of the cytosol (low water concentration) – cells lose water + shrivel (crenate)
Osmosis and Cells• Important because large volume changes caused by water movement disrupt normal cell function• Cell shrinkage or swelling – Isotonic: cell neither shrinks nor swells – Hypertonic: cell shrinks (crenation) – Hypotonic: cell swells (lysis)
Effects of Tonicity on RBCsHypotonic, isotonic and hypertonic solutions affect the fluidvolume of a red blood cell. Notice the crenated and swollencells.
Filtration• Cell membrane works like a sieve• Depends on pressure difference on either side of a partition• Moves from side of greater pressure to lower• Water and small molecules move through the pores of the membrane while large molecules don’t.• Example: urine formation in the kidneys.
Carrier Mediated Transport• Many molecules cannot enter or leave cell by diffusion• CMT utilizes proteins to carry solutes across cell membrane• Characteristics of mediated transport: 1. Specificity - each transport protein binds to and transports only a single type of molecule or ion 2. Competition - results from similar molecules binding to the same protein. 3. Saturation - rate of movement of molecules is limited by the number of available transport proteins
Membrane Carriers• Uniporter – carries only one solute at a time• Symport – carries 2 or more solutes simultaneously in same direction (cotransport)• Antiport – carries 2 or more solutes in opposite directions (countertransport) • sodium-potassium pump brings in K+ and removes Na+ from cell• Any carrier type can use either facilitated diffusion or active transport
1. When the concentration of x molecules outside the cell is low, theSaturation of a transport rate is low because it is limited by the number of molecules available to be transported.Carrier Protein 2. When more molecules are present outside the cell, as long as enough carrier proteins are available, more molecules can be transported; thus, the transport rate increases. 3. The transport rate is limited by the number of carrier proteins and the rate at which each carrier protein can transport solutes. When the number of molecules outside the cell is so large that the carrier proteins are all occupied, the system is saturated and the transport rate cannot increase.
CMT: Facilitated Diffusion• Glucose and amino acids are insoluble in lipids and too large to fit through membrane channels• Passive process, i.e. no ATP used• Solute binds to receptor on carrier protein – Latter changes shape then releases solute on other side of membrane – Substance moved down its concentration gradient
CMT: Active Transport• Uses ATP to move solutes across a membrane• It is not dependent on a [ ] gradient – Can move substances against their [ ] gradients - i.e. from lower to higher concentrations! Wow! – Allows for greater accumulation of a substance on one side of the membrane than on the other.• Carrier proteins utilized called ion or exchange pumps. – Ion pumps: actively transport Na+, K+, Ca++, Cl- – Exchange pumps: Na+-K+ pump
+ 6 Sodium-Potassium Pump K is released and Na+ Extracellular Binding1of cytoplasmic Na+ to the pump sites are ready to bind fluid protein stimulates phosphorylation by ATP. Na+ again; the cycle repeats. Cytoplasm 2 Phosphorylation causes the protein to change its shape. Concentration gradients of K+ and Na+ 3 5 The shape change expels Na+ to theLoss of phosphate restores the outside, and extracellular K+ binds.original conformation of the 4pump protein. K+ binding triggers release of the phosphate group. Figure 3.10
Functions of Na -K Pump + +• Regulation of cell volume – “fixed anions” attract cations causing osmosis – cell swelling stimulates the Na+- K+ pump to ↓ ion concentration, ↓ osmolarity and cell swelling• Heat production (thyroid hormone increase # of pumps; heat a by-product)• Maintenance of a membrane potential in all cells – pump keeps inside negative, outside positive• Secondary active transport (No ATP used) – steep concentration gradient of Na+ and K+ maintained across the cell membrane – carriers move Na+ with 2nd solute easily into cell • SGLT saves glucose in kidney
• Ions or molecules move in same (symport) or different Secondary • (antiport) direction. Is the movement of glucose a symporter example or anActive Transport • antiporter example? This example shows cotransport of Na+ and glucose. – A sodium-potassium exchange pump maintains a concentration of Na that is higher outside the cell than inside. Active transport. – Na moves back into the cell by a carrier protein that also moves glucose. The concentration gradient for Na provides the energy required to move glucose against its concentration gradient.
Vesicular Transport• Transport large particles or fluid droplets through membrane in vesicles – uses ATP• Exocytosis –transport out of cell• Endocytosis –transport into cell – phagocytosis – engulfing large particles – pinocytosis – taking in fluid droplets – receptor mediated endocytosis – taking in specific molecules bound to receptors
Vesicular Transport Endocytosis• Packaging of extracellular materials in vesicles at the cell surface• Involves relatively large volumes of extracellular material• Requires energy in the form of ATP• Three major types 1. Receptor-mediated endocytosis 2. Pinocytosis 3. Phagocytosis
Receptor Mediated Endocytosis• A selective process• Involves formation of vesicles at surface of membrane – Vesicles contain receptors on their membrane – Vesicles contain specific target molecule in high concentration• Clathrin-coated vesicle in cytoplasm – uptake of LDL from bloodstream – If receptors are lacking, LDL’s accumulate and hypercholesterolemia develops
Vesicular Transport Pinocytosis or “Cell-Drinking”• Taking in droplets of ECF – occurs in all human cells• Not as selective as ‘receptor-mediated endocytosis’• Membrane caves in, then pinches off into the cytoplasm as pinocytotic vesicle
Vesicular TransportPhagocytosis or “Cell-Eating”Keeps tissues free of debris and infectious microorganisms.
Vesicular Transport: Exocytosis• Secreting material or replacement of plasma membrane
Passive Membrane Transport – Review - Process Energy Source Example Movement of O2 through Simple diffusion Kinetic energy membraneFacilitated diffusion Kinetic energy Movement of glucose into cells Osmosis Kinetic energy Movement of H2O in & out of cells Filtration Hydrostatic pressure Formation of kidney filtrate
Active Membrane Transport – Review Process Energy Source Example Movement of ions acrossActive transport of solutes ATP membranes Exocytosis ATP Neurotransmitter secretion Endocytosis ATP White blood cell phagocytosis Fluid-phase endocytosis ATP Absorption by intestinal cells Receptor-mediated Hormone and cholesterol ATP endocytosis uptake Endocytosis via caveoli ATP Cholesterol regulationEndocytosis via coatomer Intracellular trafficking of ATP vesicles molecules