Chapter 3 Membrane Transport PDF Fall 2024

Chapter 3 The Cellular Level of Organization Cell Membranes Functions: 1. maintains the structural integrity of the cell 2. defines the boundaries of the cell and its membranous organelles 3. serves as a selective barrier allowing regulated transport in and out of the cell (or membranou...

Chapter 3 The Cellular Level of Organization Cell Membranes Functions: 1. maintains the structural integrity of the cell 2. defines the boundaries of the cell and its membranous organelles 3. serves as a selective barrier allowing regulated transport in and out of the cell (or membranous organelles) 4. allows the cell (or membranous organelles) to control the internal environment 5. contains enzymes and receptors (The plasma membrane is ~50% protein with about 50 lipid molecules per protein.) Integral Membrane Proteins classified by function… (linker) Membrane permeability… -The permeability of the cell membrane determines precisely which substances can enter or leave the cell. -A membrane that would allow any substance to cross without difficulty, is described as freely permeable. -If nothing can cross the membrane, the membrane is described as impermeable. -Cell membranes are best described as selectively permeable. -A selectively permeable (semi-permeable) membrane permits the passage of some materials and restricts the passage of others. The structure of the lipid bilayer generally restricts the passage of polar molecules. Cells may permit certain polar molecules to cross by inserting specific transport proteins or channels into the membrane. Cells (and membranous organelles) differ in their permeabilities according to variations in the organization and identity of membrane lipids and proteins. Membrane Transport Mechanisms (Passive) (Active) No ATP required What causes diffusion? All molecules exhibit random thermal motion. Solutions are “crowded”, so molecules travel only a short distance before colliding with other molecules. Elastic collisions with other molecules (like billiard balls). Produces a “random walk”. Diffusion is only effective for transport over short distances. Small molecules (O2, CO2, H2O, ions) diffuse relatively quickly Diffusion times for different distances for oxygen: x (distance) t (time) Glucose 10-4 cm = 1 m 0.17 msec ~10x 10-3 cm = 10 m 17 msec slower 10-2 cm = 100 m = 0.1 mm 1.7 sec Protein 10-1 cm = 1 mm 167 sec = 2 minutes 47 seconds ~100x 1 cm 16667 sec ≈ 4 hours 38 minutes slower Because cells are dependent upon diffusion for most processes, the diffusion rate puts a limit on cell size. Cells are typically around 10 m in diameter. Net diffusion occurs from an area of greater concentration to an area of lesser concentration. Net diffusion stops when the concentrations have reached equilibrium. (i.e. when there is no more conc gradient) Example of a concentration gradient with direction of net diffusion shown… Net diffusion of molecules across a cell membrane… Side 1 Side 2 Extracellular Intracellular solution solution Rate of net diffusion of solute across the membrane (Fick’s Law), where D = diffusion coefficient (primarily dependent on size of molecule) A = surface area of the membrane C = concentration difference across the membrane d = thickness of the membrane Membrane Transport Mechanisms (Passive) (Active) No ATP required Simple Diffusion Water, O2, CO2, and lipid soluble molecules like fatty acids and steroids can easily diffuse across the phospholipid bilayer. Facilitated Diffusion Hydrophilic molecules ( K+, Na+, Ca2+, amino acids, monosaccharides, etc.) cannot pass directly through the phospholipid bilayer. To cross the membrane, hydrophilic molecules must pass through protein channels or be transported across by protein carriers. If the hydrophilic molecules are aided through the membrane down their concentration gradient, then we call it facilitated diffusion. concentration gradient (hydrophobic molecules) (hydrophilic molecules) Carrier Proteins (also called membrane transporters) Carrier proteins have binding sites for the transported molecule. After binding the molecule, the protein changes conformation (shape) and releases the molecule on the other side of the membrane. Facilitated Diffusion Important metabolites (glucose, fatty acids, etc.) are typically acted upon in some way as soon as they enter the cell. This keeps the intracellular concentration of the metabolite low, thereby facilitating further uptake.  Summary: properties of facilitated diffusion Unlike simple diffusion, facilitated diffusion… -is mediated by membrane proteins -is highly selective to one (or a few) specific solutes -may be regulated! Acute regulation – changed quickly (usually within minutes) Chronic regulation – changed over time (usually days, weeks, months, etc…) Channels Channels form permanent water-filled pores that span the membrane. The pore of an ion channel has a selectivity filter so that only particular ions can pass through. selectivity is based on both size and charge Na+ K+ Selectivity filter An ion’s view down the channel… cross section of a sodium channel  Classification of Channels by Channel Gating Most channels can be opened or closed. Ligand This is called “channel gating”. Constitutively open (or passive) channels – such channels are almost always open (examples: water channels, K+ leak channels, Na+ leak channels) Ligand-gated channels – a specific molecule (the ligand) binds to the channel, causing it to open Phosphorylation-gated channels – open or closed according to whether the channel protein is phosphorylated Voltage-gated channels – open or closed in response to a local change in the membrane potential Mechanically-gated channels – open or closed in response to stretching or pulling forces (found in sensory receptors responding to touch, pressure, or vibration) Mechanically-gated ion channel Electrical forces contribute to the net flux of ions across the membrane. -Cells use energy to concentrate K + inside the cell and Na+ outside the cell. -K+ leakage channels (slowly conducting, but always open) allow K + to leak out of the cell down its concentration gradient. -As K+ leaves the cell down its concentration gradient, negative charges that are left behind build up along the inner membrane surface and positive charges build up along the outer membrane surface. -This separation of charges across the membrane (an electrical gradient) creates the cell membrane potential. -All cells have a membrane potential. Electrical forces contribute to the net flux of ions across the membrane. Since the cell membrane potential is negative on the inside, it will oppose the movement of K+ ions out of the cell and down their concentration gradient. At some point, the electrical gradient opposing K+ leakage will exactly balance the chemical gradient (the concentration difference) favoring K+ leakage. At this point, the net flux of K+ ions will be zero (even though there is still a concentration gradient). Since the net movement of ions across the membrane is determined by both the concentration gradient and the electrical gradient, it is more correct to say that ions diffuse according to their electrochemical gradient. Chemical gradient = concentration gradient Summary of Membrane Transport Active transport is the pumping of molecules against their electrochemical gradient with the expenditure of energy. ADP Primary active transporters (or pumps) use the energy of ATP to transport molecules against their electrochemical gradient. Example of Primary Active Transport: the Na+/K+ Pump The Na+/K+ pump uses the energy released in the hydrolysis of ATP to move K+ and Na+ across the plasma membrane against their electrochemical gradients. This pump maintains the high concentration of K+ and a low concentration of Na+ inside the cell. For every ATP, 3 Na+ ions are transported out of the cell and 2 K+ ions are transported in.  Secondary Active Transport The energy stored in an electrochemical gradient (such as the Na+ gradient) can be used to move other molecules across the cell membrane against their electrochemical gradients. The transport of the two molecules is said to be coupled. concentration gradients Na+ glucose Example: Transepithelial transport of glucose in the intestine. ADP Summary of Membrane Transport Bulk transport Vesicular Transport (or Bulk Transport) Exocytosis – moves substances out of the cell Endocytosis – moves substances into the cell Transcytosis – moves substances across a cell layer Substance (or Vesicular) Trafficking – moves substances from one area of the cell to another All require energy. ….a membrane-bound vesicle Vesicular Transport: Exocytosis In exocytosis, intracellular vesicles fuse with the plasma membrane, spilling the contents of the vesicle out of the cell. requires Ca2+ Vesicular Transport: Endocytosis Endocytosis – the import of materials into the cell by infoldings in the plasma membrane. phagocytosis (cell eating) pinocytosis (cell drinking) receptor-mediated endocytosis Phagocytosis.... absorb nutrients Vesicular Trafficking In many cell types (esp. neurons and fibroblasts) motor molecules called kinesins and dyneins carry loaded vesicles along microtubules. Kinesin in motion….