CellMembranes_KJ_F2024_STUDENTS.pdf

Cell Membranes  Contact Karron J. James, Ph.D. Professor, Dept. of Biochemistry, Cell Biology, & Genetics Office: GB6, Block B Email: [email protected] Phone 484-8900 ext 1041 Office hours: Mon-Fri, 2-4pm or by appointment  Reading assignments Albert...

Cell Membranes  Contact Karron J. James, Ph.D. Professor, Dept. of Biochemistry, Cell Biology, & Genetics Office: GB6, Block B Email: [email protected] Phone 484-8900 ext 1041 Office hours: Mon-Fri, 2-4pm or by appointment  Reading assignments Alberts, et al., Molecular Biology of the Cell, 4ed. Ch 10, 11: Membrane Structure (first two paragraphs) Membrane Lipids Are Amphipathic Molecules, Most of which Spontaneously Form Bilayers (2nd paragraph) The Fluidity of a Lipid Bilayer Depends on Its Composition (3rd, 5th paragraphs) Membrane Proteins Membrane Proteins Can Be Associated with the Lipid Bilayer in Various Ways (first two paragraphs) Principles of Membrane Transport Protein-free Lipid Bilayers Are Highly Impermeable to Ions There Are Two Main Classes of Membrane Transport Proteins: Carriers and Channels Active Transport Is Mediated by Carrier Proteins Coupled to an Energy Source  Reading assignments Alberts et al., Molecular Biology of the Cell, 4ed. Ch 13: Transport into the Cell from the Plasma Membrane: Endocytosis Specialized Phagocytic Cells Can Ingest Large Particles (first 3 paragraphs) Cells Import Selected Extracellular Macromolecules by Receptor-mediated Endocytosis (first 3 paragraphs) Specific Proteins Are Removed from Early Endosomes and Returned to the Plasma Membrane Transport from the Trans Golgi Network to the Cell Exterior: Exocytosis Many Proteins and Lipids Seem to Be Carried Automatically from the Golgi Apparatus to the Cell Surface Secretory Vesicles Bud from the Trans Golgi Network (1st paragraph)  Goal MCB.11. Understand the importance of the cell membrane and its components to the overall functioning of cells Learning Objectives Given a scenario, image, or graph, students should be able to: MCB.11.1. Recognize the location and significance of different types of lipids and proteins that constitute a biological membrane MCB.11.2. Distinguish the type of transport—diffusion, osmosis, facilitated diffusion, primary and secondary active transport, exocytosis, endocytosis, or transcytosis.  Goal MCB.11. Understand the importance of the cell membrane and its components to the overall functioning of cells Learning Objectives Given a scenario, image, or graph, students should be able to: MCB.11.1. Recognize the location and significance of different types of lipids and proteins that constitute a biological membrane MCB.11.2. Distinguish the type of transport—diffusion, osmosis, facilitated diffusion, primary and secondary active transport, exocytosis, endocytosis, or transcytosis.  Membranes—General Overview Includes plasma and organelle membranes Primarily lipids (40-80%; Fig. 10-1. Alberts. amphipathic), proteins Bilayer—2 monolayers (leaflets). Fluid mosaic model Asymmetric Adapted from: Figure 3.7. Lippincott® Illustrated Reviews: Cell and Molecular Biology, 3e, 2024 LIPIDS  Membrane Lipid Organisation Each layer is referred to as a leaflet www.saddlespace.org  Membrane Lipids—Phospholipids Glycerophospholipids/ phosphoglycerides – Phosphatidylcholines (PC), phosphatidylserines (PS), phosphatidylethanolamines (PE), phosphatidylinositols (PI) PC (lecithin), mainly in outer http://www.bioinfo.org.cn/book/biochemistry/chapt09/sim2.htm leaflet PE, PI mainly in inner leaflet PS exclusively in inner leaflet  Membrane Lipids—Sphingolipids Located mainly in outer leaflet Derived from ceramide Major component of lipid rafts en.wikipedia.org  Membrane Lipids—Glycolipids Glycolipids – Most made from ceramide: glycosphingolipids – Eg. gangliosides, ABO blood group Ags http://www.bioinfo.org.cn/book/biochemistry/chapt09/sim2.htm – Minor but essential; ~2% of membrane lipids – Exclusive to outer leaflet Cooper and Hausman. ‘The Cell—A Molecular Approach’. 4 ed.  Membrane Lipids—Cholesterol Amphipathic Interdigitates between phospholipids in inner and cyjezyk.github.com outer leaflets Helps maintain fluidity/ structural integrity of plasma membrane Major component of lipid rafts What about triglycerides? http://www.bioinfo.org.cn/book/biochemistry/chapt09/sim2.htm Plasma Membrane is Asymmetric Normal membrane Abnormal membrane Red: PC Burgundy: SM Yellow: PE Green: PS From Fig 2-10. Goodman, B. (2008). Medical Cell Biology. Academic Press. Fig 10-14. Alberts. PROTEINS  Membrane Proteins Integral, peripheral (membrane associated) All TM proteins integral Time for RETRIEVAL PRACTICE https://www.bookwidg ets.com/play/Ef4oAHx-- iQAFfTBwOgAAA/YE7ZV YJ/membrane-lipids  Membranes—Review Figure 3.7. Lippincott® Illustrated Reviews: Cell and Molecular Biology, 3e, 2024  Goal MCB.11. Understand the importance of the cell membrane and its components to the overall functioning of cells Learning Objectives Given a scenario, image, or graph, students should be able to: MCB.11.1. Recognize the location and significance of different types of lipids and proteins that constitute a biological membrane MCB.11.2. Distinguish the type of transport—diffusion, osmosis, facilitated diffusion, primary and secondary active transport, exocytosis, endocytosis, or transcytosis. MEMBRANE PROTEINS & TRANSPORT  Transport Across Membranes Selectively permeable barrier Main modes of transport: – osmosis, simple diffusion, facilitated transport, active transport, exocytosis, endocytosis, transcytosis Size exclusion limit  Simple Diffusion Small, lipid-soluble http://69.36.35.38/accp/pccsu/inhaled-nitric-oxide-therapeutic-uses-and-potential-hazards?page=0,3 molecules can diffuse through membrane according to their concentration gradient Movement in both directions but net flow in one direction until concentration on both sides of membrane equal – Eg. NO diffuses through lipid bilayer  Osmosis Aquaporins—channels used for transport of water – Integral membrane proteins wwwuser.gwdg.de  Facilitated Diffusion Some molecules too large, charged or hydrophilic→ cannot simply diffuse through lipid bilayer Carrier proteins (transmembrane proteins) change conformation to rapidly move a molecule across the membrane, down its electrochemical gradient (Passive transport) bya.dromgip.top  Active Transport ENERGY used to transport molecules across membrane Primary active transport Secondary active transport; co-transport http://igbiologyy.blogspot.com/2012/12/19-active-transport_5.html  Active Transport— Primary Active Transport Eg. Na/K ATPase, expressed in most cells – Pumps Na+ ions out of cell and K+ ions into cell, with hydrolysis of ATP, ie. against each ion’s electrochemical gradient NOTE: [Na+] in the ECF than in the ICF; [K+] higher in the ICF Fig 11-15. Alberts. 6ed.  Active Transport— Secondary Active Transport Transport of one molecule coupled to movement of another molecule (co- transport) Symport Antiport Goodman, S.R. Medical Cell Biology. 3ed.  Active Transport— Secondary Active Transport Eg. Na/Glucose, SGLT1; symport – Both glucose and Na+ bind symporter and are transported into cell – Energy from Na+ moving down its electrochemical gradient is maintained by Na/K ATPase – Na+ and glucose in intestinal lumen are transported across apical membrane of enterocytes into these cells, against glucose concentration Fig 11-11. Alberts. 6ed. gradient  Ion Channels Transmembrane proteins that form aqueous conduits, selective for types of charged species that can flow through them (passive transport) Move ions at relatively high rate – Examples: conduction of nerve impulses, muscle contraction (FYI: Not permanently open—many are gated, ie. they open and close in response to specific stimuli)  Ion Channels—Gating Permeability of membranes must be regulated Three major classes of gated channels: – Voltage-, ligand-, mechanically-gated  Ion Channels—Voltage-gated Channels Open in response to change in electrical potential across cell membrane Fig 11-22. Alberts. 6ed  Ion Channels Gap junctions – Allow passage of ions, other solutes  Ion Channels—Ligand-gated Channels Open in response to reversible binding of chemical molecules – Eg. acetylcholine Fig 11-22. Alberts. 6ed.  CFTR Anion channel Chloride, bicarbonate Cl- Cl- Cl- Cl- extracellular cytosol ATP ATP Created with BioRender.com  Your Patient A 15-year-old male is brought to the physician because of shortness of breath during a sporting activity. He was diagnosed with cystic fibrosis at 3 months of age based on typical clinical manifestations and results from a sweat test. His history is significant for multiple respiratory tract infections.  Ion Channels—Mechanosensitive Open in response to mechanical forces Fig 11-22. Alberts. 6ed. Time for RETRIEVAL PRACTICE https://www.bookwidg ets.com/play/zAr7o0a_- iQAE7YyI5gAAA/LFSRAL H/membrane-protei  Goal MCB.11. Understand the importance of the cell membrane and its components to the overall functioning of cells Learning Objectives Given a scenario, image, or graph, students should be able to: MCB.11.1. Recognize the location and significance of different types of lipids and proteins that constitute a biological membrane MCB.11.2. Distinguish the type of transport—diffusion, osmosis, facilitated diffusion, primary and secondary active transport, exocytosis, endocytosis, or transcytosis.  Exocytosis Cell releases molecules into extracellular environment through fusion of transport vesicles with plasma membrane Material to be exocytosed may From Fig 13-54. Alberts, Molecular Biology of The Cell, 4ed. be synthesized and: – Released immediately from cell, – Stored in secretory vesicles near the membrane until needed. Eg. Neurotransmitters, hormones – …Or, synthesized as precursors. When needed, converted to active proteins before or after exocytosishttps://www.euroimmunblog.com/diabetes-mellitus-in-focus-of-world-health-day-  Endocytosis Cell takes up macromolecules, fluid, solutes, membrane components Phagocytosis, pinocytosis Material enclosed by plasma membrane which eventually pinches off to form endocytic vesicle http://apbiology11.weebly.com/endocytosis.html (EV)  Endocytosis EV may fuse with receiving compartment→ early endosome (EE) – sorting→ recycling, degradation, other Endosome maturation: EE→→ LE Fusion of LE with lysosomes→ Fig 13-42. Alberts. 6ed. endolysosomes; degradation  Receptor-mediated Endocytosis Some endocytosis events (incl. phagocytosis) require binding of extracellular macromolecule to a membrane-bound receptor Example: Cholesterol (LDL) taken up from bloodstream via RME Fig 13-46. Alberts.  Phagocytosis Endocytosis of large particle followed by fusion with specialized vesicle → phagosome – Bacteria, viruses, apoptotic cells Phagosome fuses with lysosome and ingested material is degraded Phagocytosis performed by specialized cells, such as Fig 13-42. Alberts. 6ed. macrophages, neutrophils and osteoclasts  Transcytosis Vesicle-mediated transcellular transport Figure 13-45 Possible fates for transmembrane receptor proteins that have been endocytosed. Three pathways from the endosomal compartment in an epithelial cell are shown. Retrieved receptors are returned (1) to the same… (see textbook for complete figure legend)  Goal MCB.11. Understand the importance of the cell membrane and its components to the overall functioning of cells Learning Objectives Given a scenario, image, or graph, students should be able to: MCB.11.1. Recognize the location and significance of different types of lipids and proteins that constitute a biological membrane MCB.11.2. Distinguish the type of transport—diffusion, osmosis, facilitated diffusion, primary and secondary active transport, exocytosis, endocytosis, or transcytosis. A 55-year-old woman presents to her physician with complaints of substernal chest pain while at rest. Upon physical examination, the physician notes that her heartbeat is less rhythmic than it should be. A defect in diffusion of ions between adjacent affected cardiac myocytes is identified. Expression of the gene coding for which of the following is most likely affected? A) Aquaporin B) Calcium ATPase C) Gap junction D) GLUT2 E) Na/K ATPase