NURS 230 TRW Lec3a Cell Membranes PDF

Topic 3 (part 1): Introduction to Cells and Cell membranes https://janiesplace.wordpress.com/tag/cell-biology-jokes/ CHAPTER 3 IN TEXT Important Topics and Pages Topic 3: Cells (Chapter 3) (Part 1 is Cell Membranes) 1. List the parts of the cell membrane and their functions (t...

Topic 3 (part 1): Introduction to Cells and Cell membranes https://janiesplace.wordpress.com/tag/cell-biology-jokes/ CHAPTER 3 IN TEXT Important Topics and Pages Topic 3: Cells (Chapter 3) (Part 1 is Cell Membranes) 1. List the parts of the cell membrane and their functions (this includes the phospholipids and different types of membrane proteins and their functions) P 63-68, 81 2. List the different ways substances are transported across cell membranes 3. What is the difference between Passive and Active Processes P 68 4. Explain the main types of diffusion using examples (Simple, facilitated, osmosis) P 68-72 5. Explain the different active membrane transport processes (active transport, vesicular transport) P 73-79 6. Be able to explain how the sodium-potassium pump works P 74 7. Explain the effects of Cystic Fibrosis on the normal physiology, in particular homeostasis, cell membranes and proteins Introduction: Cells ◦ A cell is the structural and functional unit of life ◦ Understanding cells is essential to human health and disease ◦ Structure and function are complementary ◦ Biochemical functions of cells are dictated by shape of cell and specific subcellular structures ◦ Cell membranes are very important for physiological processes ◦ Permeability important for treatments  Cell diversity Over 200 different types of human cells Types differ in size, shape, and subcellular components ◦ These differences lead to differences in functions Figure 3.1 © 2016 PEARSON EDUCATION, INC.  General Cell ◦ All cells have some common structures and functions ◦ Human cells have three basic parts: 1. Plasma membrane: flexible outer boundary 2. Cytoplasm: intracellular fluid containing organelles 3. Nucleus: DNA containing control Figure 3.2 center  Extracellular Materials Substances found outside cells Classes of extracellular materials include: ◦ Extracellular fluids (body fluids) ◦ Eg. Blood plasma, cerebrospinal fluid https://www.researchgate.net/figure/284728652_fig5_Figure-1-The-combinatorial- extracellular-matrix-ECM-of-bone-A-range-of-biological ◦ Cellular secretions (e.g., saliva, mucus) ◦ Extracellular matrix: substance that acts as glue to hold cells together http://biotestplasma.com/frequently-asked-questions/ Plasma membrane Acts as an active barrier separating intracellular fluid (ICF) from extracellular fluid (ECF) Plays dynamic role in cellular activity by controlling what enters and what leaves cell Also known as the “cell membrane”  Plasma Membrane Structure Consists of membrane lipids (phospholipids) that form a flexible lipid bilayer Specialized membrane proteins float through this fluid membrane, resulting in constantly changing patterns ◦ Referred to as fluid mosaic model (made up of many moving pieces) Surface sugars form coating known as glycocalyx ◦ Different combinations in the glycocalyx allows for identification of different cells Membrane structures help to hold cells together through cell junctions Focus Figure 3.1 4 major functions of the Plasma Membrane 1. Physical Barrier 2. Selective Permeability 3. Communication 4. Cell Recognition Focus Figure 3.1  Membrane Lipids Lipid bilayer is made up of: 75% phospholipids, which consist of two parts: ◦ Phosphate heads: are polar (charged), so are hydrophilic (water- loving) ◦ Fatty acid tails: are nonpolar (no charge), so are hydrophobic (water-hating) ◦ *Remember: phobia is when you are afraid of something © 2016 PEARSON EDUCATION, INC. Membrane Lipids (cont.) ◦5% glycolipids ◦ Lipids with sugar groups on outer membrane surface https://phys.libretexts.org/LibreTexts/ University_of_California_Davis/UCD%3A_Biophysics_241/ Lipids_Types/Glycolipids ◦20% cholesterol ◦ Increases membrane https:// stability (stiffens the cranemedicine.wordpress.co membrane) m/ 2015/05/12/ the-biology-of- stress-and- depression-pt- 6-the- cholesteroldop amine- connection/  Membrane Proteins: Integral proteins ◦ Firmly inserted into membrane ◦ Most are transmembrane proteins (span the plasma membrane) ◦ Have both hydrophobic and hydrophilic regions ◦ Hydrophobic residues are embedded in membrane (coils in the figure) ◦ Hydrophilic residues are in the intra- and extracellular space (loops in the figure) http://www.proteinatlas.org/humanproteome/secretome ◦ Function as transport proteins (channels and carriers), enzymes, or receptors  Membrane Proteins: Peripheral proteins ◦ Loosely attached to integral proteins or the membrane ◦ Include filaments on intracellular surface used for plasma membrane support ◦ Function as: ◦ Enzymes ◦ Motor proteins for shape change during cell division and muscle contraction http://physiologyplus.com/membrane-proteins/ ◦ Cell-to-cell connections ◦ The next slides will address 6 major functions of membrane proteins  Functions of Membrane proteins Figure 3.3 © 2016 PEARSON EDUCATION, INC. Functions of Membrane proteins Signal Receptors for signal transduction A membrane protein exposed to the outside of the cell may have a binding site that fits the shape of a specific chemical messenger, such as a hormone. When bound, the chemical messenger may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell. Receptor Membrane Receptors: Important in Cell Signalling Ligands: molecules that bind to receptors (hormones, Ligand neurotransmitters, growth factors, etc.) Binding of ligand leads to Receptor downstream signalling cascade Eg. G protein-linked receptors, insulin receptor, TGF beta receptor, interferon receptors, etc. Functions of Membrane proteins Attachment to the cytoskeleton and extracellular matrix Ele­ments of the cytoskeleton (cell’s internal supports) and the extracellular matrix (fibers and other substances outside the cell) may anchor to membrane proteins, which helps main­tain cell shape and fix the location of certain membrane proteins. Others play a role in cell movement or bind adjacent cells together. Functions of Membrane proteins Enzymatic activity Enzymes A membrane protein may be an enzyme with its active site exposed to substances in the adjacent solution. A team of several enzymes in a membrane may catalyze sequential steps of a met­abolic pathway as indicated (left to right) here. Functions of Membrane proteins Intercellular joining (Cell-to-cell joining) Membrane proteins of adjacent cells may be hooked together in various kinds of intercellular junctions. Some membrane proteins (cell adhesion molecules or CAMs) of this group provide temporary binding sites that guide cell migration and other cell-to-cell interactions. CAMs Functions of Membrane proteins Cell-cell recognition Some glycoproteins (proteins bonded to short chains of sugars which help to make up the glycocalyx) serve as identification tags that are specifically recognized by other cells. Glycoprotein Glycocalyx Consists of sugars (carbohydrates) sticking out of cell surface (extracellular) ◦ Attached to proteins (glycoproteins) and lipids (glycolipids) Every cell type has different patterns of this “sugar coating” ◦ Functions as specific biological markers for cell- to-cell recognition Can you think of why/ ways this is important in health and disease? What might happen if there were problems with Glycocalyx? Cell Junctions Most cells are bound together to form tissues and organs ◦ (Some cells which are “free” include red blood cells, lymphocytes, etc) Three ways cells can be bound to each other ◦ Tight junctions ◦ Desmosomes ◦ Gap junctions  Tight junctions ◦ Integral proteins on adjacent cells fuse to form an impermeable junction that encircles whole cell ◦ Prevent fluids and most molecules from moving in between cells ◦ Creates continuous seal around cells ◦ Where might these be useful in body? ◦ Think: Ziploc® bag seal Figure 3.4  Desmosomes ◦ Formed when linker proteins (cadherins) of neighboring cells interact with similar types of linker proteins ◦ Linker protein is anchored to its cell through thickened plaques (on cytoplasmic surface) ◦ Keratin filaments anchor plaques to internally ◦ Where might these be useful in body? ◦ Think: Velcro® Figure 3.4 Gap junctions ◦ Transmembrane proteins (connexons) allow small molecules to pass from cell to cell ◦ Used to spread ions, simple sugars, or other small molecules between cells ◦ Allows electrical signals to be passed quickly from one cell to next cell (communication) Figure 3.4 ◦ Used in cardiac and smooth muscle cells Review Questions What are some of the functions of cell-surface proteins? What is a glycocalyx and what are its functions? What are the 3 different types of cell junctions? Membrane Transport Plasma membranes are selectively permeable ◦ Some molecules pass through easily; some do not Two ways substances cross membrane ◦ Passive processes: no energy required ◦ Active processes: energy (ATP) required Passive Membrane Transport Two types: Diffusion ◦ Simple diffusion ◦ Carrier- and channel- mediated facilitated diffusion ◦ Osmosis Filtration ◦ Type of transport that usually occurs across capillary walls (discuss more in cardiovascular section) https://www.pinterest.com/pin/298996862744191435/  Diffusion Molecules move from high concentration to low concentration ◦ Concentration gradient: difference in concentrations Diffusion: down concentration gradient (high to low) http://www.healthline.com/health-news/dangers-of-secondhand-smoke-in-apartments-condominiums Speed of diffusion ◦ Size of molecule ◦ Temperature ◦ Concentration Eg. Smoke filling room, Dye in water Figure 3.5 Diffusion Thought Question Non-living tubing in beaker has permeable membrane (pores) 10% NaCl, 5% Glucose Solution Which direction will NaCl 20% NaCl Solution, 2% Glucose Solut move? Glucose? Diffusion in Cells Plasma membranes can form barrier, stop diffusion of most solutes ◦ Selectively permeable Very small, lipid soluble may freely pass through: passive diffusion (simple diffusion) Remember, inner membrane hydrophobic Eg. O2, CO2, fatty acids, some steroid hormones Figure 3.6 Passive Diffusion Video © 2016 PEARSON EDUCATION, INC. Passive Diffusion Example: Estrogen Signalling Estrogen and other steroids are small, lipid soluble Can pass through membrane, bind to receptors in cell Important aspect of hormone signalling http://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(12)00244-4 Facilitated Diffusion Some hydrophobic molecules transported passively down concentration gradient ◦Eg. Glucose, amino acids, ions Two types of facilitated diffusion: 1. Carrier-mediated facilitated diffusion ◦ Substances bind to protein carriers in membrane 2. Channel-mediated facilitated diffusion ◦ Substances move through channel proteins, or water-filled channels Facilitated Diffusion: Carrier-Mediated Diffusion Carrier: transmembrane integral protein ◦ Transport polar, larger molecules eg. Sugars, amino acids Binding of molecule causes carrier to change shape, moving molecule Molecule still moves down the concentration gradient Carriers can become saturated Figure 3.6  Facilitated Diffusion: Channel-Mediated Channel: aqueous-filled transmembrane protein Transport small, lipid-insoluble molecules down concentration gradient ◦ Specificity based on pore size and/or charge Two types: ◦ Leakage channels ◦ Always open ◦ Gated channels ◦ Controlled by chemical or electrical signals Figure 3.6v Facilitated Diffusion: Channel-Mediated Osmosis Water so small, also can diffuse through membrane Also, channels which allow water to diffuse: aquaporins Aquaporins important in kidneys, blood cells, other tissues, regulate water balance Movement of solvent down concentration gradient: osmosis Figure 3.6 Osmosis Osmolarity: measure of total concentration of solute particles Solute concentration increases, water concentration decreases Water moves by osmosis from areas of low solute (high water) concentration to high areas of solute (low https://www.pinterest.com/pin/164170348890094275/ water) concentration Osmosis Solutes and water move across permeable membrane Movement occurs until equilibrium reached Figure 3.7 Osmosis When membrane only permeable to water, osmosis occurs, volume will change Figure 3.7  Osmosis Movement of water causes pressures: ◦Hydrostatic pressure: pressure of water inside cell pushing on membrane ◦Osmotic pressure: tendency of water to move into cell by osmosis ◦ The more solutes inside a cell, the higher the osmotic pressure A living cell has limits to how much water can enter it Water also leaves cells Change in cell volume can disrupt cell function, especially in neurons Osmosis: Tonicity Relative terms Isotonic solution has same osmolarity as inside the cell, volume remains unchanged (iso = equal) Hypertonic solution has higher osmolarity than inside cell, water flows out of cell ◦ Shrinking is referred to as crenation Hypotonic solution has lower osmolarity than inside cell, water flows into cell ◦ Can lead to cell bursting, referred to as lysing See next slide for schematic showing tonicity Tonicity Example: Red Blood Cells Figure 3.8 Osmosis Thought Questions Cube membranes are only permeable to water Which solutions are hypotonic, hypertonic, isotonic to cubes? Which cubes will gain weight, which will lose? A B C D Osmosis Thought Questions Saltwater fish live in a hypertonic environment Freshwater fish live in a hypotonic environment How do you think they adapt to this? Clinical – Homeostatic Imbalance Intravenous solutions of different tonicities can be given to patients suffering different ailments ◦ Isotonic solutions are most commonly given when blood volume needs to be increased quickly ◦ Hypertonic solutions are given to edematous (swollen) patients to pull water back into blood ◦ Hypotonic solutions should not be given because they can result in dangerous lysing of red and white blood cells  Active Membrane Transport Two major active membrane transport processes ◦ Active transport ◦ Vesicular transport Both require ATP to move solutes across a plasma membrane because: ◦ Solute is too large for channels, or ◦ Solute is not lipid soluble, or ◦ Solute is moving against its concentration gradient Remember: Active requires ATP, Passive does not  Active Transport Requires carrier proteins (solute pumps) ◦ Bind specifically and reversibly with substance being moved ◦ Some carriers transport more than one substance ◦ Symporters transport two different substances in the same direction ◦ Antiporters transport one substance into cell while transporting a different substance out of cell https://en.wikipedia.org/wiki/Symporter Moves solutes against their concentration gradient (from low to high) ◦ This requires energy (ATP) Active Transport (cont.) Two types of active transport: ◦ Primary active transport ◦ Required energy comes directly from ATP hydrolysis ◦ Secondary active transport (cotransport) ◦ Required energy is obtained indirectly from ionic gradients created by primary active transport Active Transport (cont.) Primary active transport ◦ Energy from hydrolysis of ATP causes change in shape of transport protein ◦ Shape change causes solutes (ions) bound to protein to be pumped across membrane ◦ Example of pumps: calcium, hydrogen (proton), Na+-K+ pumps Active Transport (cont.) Sodium-potassium pump ◦ Most studied pump ◦ Basically is an enzyme, called Na+-K+ ATPase, that pumps Na+ out of cell and K+ back into cell ◦ Located in all plasma membranes, but especially active in excitable cells (nerves and muscles) Example: Sodium-Potassium Pump Focus Figure 3.2 Example: Sodium-Potassium Pump © 2016 PEARSON EDUCATION, INC. © 2016 PEARSON EDUCATION, INC. Focus Figure 3.2 Example: Sodium-Potassium Pump Focus Figure 3.2 Example: Sodium-Potassium Pump Focus Figure 3.2 Example: Sodium- Potassium Pump Focus Figure 3.2 Active Transport: Secondary Active Transport Depends on ion gradient that was created by primary active transport system Energy stored in gradients is used indirectly to drive transport of other solutes ◦ Eg. Low Na+ concentration that is maintained inside cell by Na +-K+ pump ◦ Na+ can drag other molecules with it as it flows into cell through carrier proteins ◦ Some sugars, amino acids, and ions transported into cells this way Figure 3.9 Secondary active transport is driven by the concentration gradient created by primary active transport. Extracellular fluid Glucose Na+ Na+ Na + Na+ Na -glucose + Na+-glucose Na + Na+ symport transporter Na+ symport Na+ transporter releases glucose Na+ into the cytoplasm Na+ loads glucose K+ from extracellular Na+-K+ fluid pump ATP Na+ Cytoplasm 1 Primary active transport 2 Secondary active transport The ATP-driven Na -K pump+ + As Na+ diffuses back across the membrane stores energy by creating a steep through a membrane cotransporter protein, it concentration gradient for Na+ drives glucose against its concentration gradient entry into the cell. into the cell. Vesicular Transport Second type of Structure of a Vesicle active membrane transport Involves transport of large particles, macromolecules, and fluids across membrane in vesicles https://en.wikipedia.org/wiki/Vesicle_(biology_and_chemistry) Requires cellular energy (usually ATP) Vesicular Transport (cont.) Vesicular transport processes include: ◦Endocytosis: transport into cell (endo = within) ◦ 3 different types of endocytosis: phagocytosis, pinocytosis, receptor-mediated endocytosis ◦Exocytosis: transport out of cell (exo = outside) ◦Transcytosis: transport into, across, and then out of cell ◦Vesicular trafficking: transport from one area or organelle in cell to another Vesicular Transport: Endocytosis ◦ Involves formation of protein-coated vesicles ◦ Usually involve receptors; therefore can be a very selective process ◦ Substance being pulled in must be able to bind to its unique receptor ◦ Some pathogens are capable of hijacking receptor for transport into cell ◦ Once vesicle is pulled inside cell, it may: ◦ Fuse with lysosome or ◦ Undergo transcytosis Vesicular Transport (cont.) Phagocytosis: type of endocytosis that is referred to as “cell eating” ◦ Pseudopods form and engulf particles ◦ Formed vesicle is called a phagosome ◦ Phagocytosis is used by macrophages and certain other white blood cells ◦ Phagocytic cells move by amoeboid motion Figure 3.11 White blood cell (neutrophil), engulfing bacteria https://youtu.be/JnlULOjUhSQ Vesicular Transport (cont.) Pinocytosis: “cell drinking” or fluid-phase endocytosis ◦Plasma membrane infolds, fluids inside cell ◦ Fuses with endosome ◦Used by some cells to “sample” environment ◦Nutrient absorption in small intestine Figure 3.11 ◦Membrane components recycled back to membrane  1 Coated pit Extracellular fluid ingests substance. Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein-coated vesicle detaches. 3 Coat proteins are recycled to plasma membrane. Transport vesicle Figure 3.10 Events of Uncoated Endosome endocytic vesicle endocytosis 4 Uncoated vesicle fuses with a sorting vesicle called an 5 Transport vesicle endosome. containing membrane Lysosome components moves to the plasma membrane for recycling. 6 Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its (a) contents to the plasma (b) membrane on the opposite side of the cell (transcytosis). Exocytosis Process where material is ejected from cell (exo=out, endo=in) ◦ Usually activated by cell-surface signals or changes in membrane voltage Substance being ejected is enclosed in secretory vesicle Some substances: hormones, neurotransmitters, mucus, cellular wastes  Exocytosis Extracellular Plasma membrane The process of fluid SNARE (t-SNARE) exocytosis Secretory vesicle – contains the substance to Secretory vesicle Vesicle 1 The membrane- bound vesicle migrates SNARE be removed from the cell (v-SNARE) Molecule to to the plasma membrane. be secreted Cytoplasm Secretory vesicle is protein coated 2 There, proteins at Protein on vesicle called Fused v- and t-SNAREs the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma v-SNARE finds and membrane proteins). hooks up to target t- Figure 3.12 SNARE proteins  Extracellular Plasma membrane The process of fluid SNARE (t-SNARE) exocytosis Secretory 1 The membrane- Vesicle Exocytosis vesicle bound vesicle migrates SNARE (v-SNARE) to the plasma membrane. Molecule to be secreted Cytoplasm Docking process forms a pore, which triggers Fused v- and 2 There, proteins at the vesicle surface (v-SNAREs) bind with exocytosis (the release t-SNAREs t-SNAREs (plasma membrane proteins). of vesicular materials) Fusion pore formed 3 The vesicle and plasma membrane fuse and a pore opens up. 4 Vesicle contents are released to the cell © 2016 PEARSON EDUCATION, INC. exterior. Table 3.3 – summary resource Review Questions What is the difference between active and passive membrane transport? ◦ What are some examples of active and passive processes? If is cell engulfs a liquid into a vesicle and transports in into the cell, what process is occurring? Briefly describe the process of the sodium-potassium pump