Membranes (SH2024) for notes1.pptx

CMM 577 Principles of Cell Biology Fall 2024 Dr. Shanna Hamilton Assistant Professor, Department of Cellular and Molecular Medicine [email protected] Hamilton Section 1. Intro and Membranes (Aug 27) 2. Protein sorting 1 – ER (Aug 29) 3. Protein sorting 2 – vesicular trafficking...

CMM 577 Principles of Cell Biology Fall 2024 Dr. Shanna Hamilton Assistant Professor, Department of Cellular and Molecular Medicine [email protected] Hamilton Section 1. Intro and Membranes (Aug 27) 2. Protein sorting 1 – ER (Aug 29) 3. Protein sorting 2 – vesicular trafficking (Sept 3) 4. Journal club (Sept 5) 5. Part of Exam 1 (Sep 26) Core reading https://ebookcentral.proqu est.com/lib/uaz/reader.acti on?docID=5320520&ppg= 1 Online version available at UA libraries Hamilton section: Chapters 10-13 Journal Club – Sept 5 Paper Commentary Primer – strongly recommended  TOPIC: Membranes LESSONS: Overview of Cells Overview of Membranes Lipid Molecules Membrane Dynamics Membrane Proteins and Membrane Transport Learning Outcomes 1. Explain the main functions of the major organelles in the cell 2. Briefly describe the structural support for the cell (cytoskeletal elements) Structure of a Eukaryotic Cell Membrane-enclosed compartments https://openstax.org/details/books/anatomy-and-physiology. Fig 3.13 Nucleus ‘Command center’ of a eukaryotic cell Stores DNA Directs synthesis of proteins and non-coding RNAs https://openstax.org/details/books/concepts_biology; Fig. 3.10 Endomembrane System Works together to modify, package and transport lipids and proteins https://openstax.org/details/books/anatomy-and-physiology; Fig. 404 Endoplasmic Reticulum (ER) Rough ER Studded with ribosomes Synthesizes proteins and phospholipids Smooth ER Few or no ribosomes Synthesizes carbohydrates, lipids (including phospholipids), and steroid hormones Stores calcium ions Pollard, et al., Cell Biology, 3rd Ed., Fig. 20.1 Specialized sarcoplasmic reticulum Abundant, modified smooth ER called SR Crucial function as a calcium store Transverse Sarcoplasmic Sarcolemma (T) tubules reticulum Nucleus Myofibrils Sarcomere Hamilton et al. (2020) Basic Res Cardiol Golgi Apparatus (Golgi Body) Sorts, packages, and tags molecules for transport https://openstax.org/details/books/anatomy-and-physiology; Fig. 404 Image from Biorender, adapted from Lodish (2013) Molecular cell biology. Lysosomes Cell’s ‘garbage disposal’ Low pH Many hydrolytic enzymes https://micro.magnet.fsu.edu/cells/lysosomes/lysosomes.html; Fig. 1 Mitochondria Cell’s ‘powerhouse’ Generate ATP by aerobic respiration Have own DNA Pollard, et al., Cell Biology, 3rd Ed.; Fig. 19.1, 19.2 Interior Framework of the Cell Cytoskeleton Network of protein fibers Maintain the cell’s shape Secures organelles Dynamic 3 types of fibers Actin filaments Microtubules Intermediate filaments https://schoolbag.info/biology/living/31.html. Fig 4.8  TOPIC: Cell Membranes LESSONS: Overview of Cells Overview of Membranes Lipid Molecules Membrane Dynamics Membrane Proteins and Membrane Transport Learning Outcomes 1. Describe the distribution of membrane-based structures within eukaryotic cells 2. Explain the utility to cells of lipid-based membranes Reminder.... Membrane-enclosed compartments https://openstax.org/details/books/anatomy-and-physiology. Fig 3.13 Membranes - relative amounts Note: cell type variability Molecular Biology of the Cell, 6th Ed. Table 12-2 Why Membranes? Partitioning confine/concentrate separate create unique cell contents inside from environment outside within cells Note: there is also intra-cellular partitioning that occurs without membrane enclosure (P-bodies, aggresomes, etc.) Lipid Bilayers Basis of biological membranes >109 lipid molecules/cell ≈5 nm thick Molecular Cell Biology, 5th Ed. Lipid Bilayers Basis of biological membranes Pollard, et al., Cell Biology, 3rd Ed., Fig. 1.10 What is it like inside a cell? Examples of the crowded complexity - scale drawing: RNA Other proteins Ribosomes Other proteins Pollard, et al., Cell Biology, 3rd Ed., Fig. 3.27  What is it like inside a cell? Examples of the crowded complexity: Interactive highlighting of specific proteins: https://www.cellsignal.com/pathways/cellular-landscapes/cellular-landscape-protein-synthesis?_requestid=1011766#  TOPIC: Cell Membranes LESSONS: Overview of Cells Overview of Membranes Lipid Molecules Membrane Dynamics Membrane Proteins and Membrane Transport Learning Outcomes 1. Explain the unique properties of lipid molecules and why they are well-suited for incorporation into biologic membranes 2. Describe the properties and features of the major types of lipid molecules in membranes 3. Explain the concept of asymmetry in membranes and its significance Lipid Bilayers Why lipids? Phospholip id The major lipid components of membranes are amphipathic Hydrophobic core in a bilayer prevents diffusion of water- soluble materials Very stable and chemically- resistant Self assemble – energetically favorable https://openstax.org/details/books/anatomy-and-physiology. Fig 3.2 Phosphoglycerides Most abundant lipids in the membrane Glycerol backbone Different ‘head groups’ with distinct properties Pollard, et al., Cell Biology, 3rd Ed., Fig. 13.2 Sphingolipids Sphingosine backbone Mostly saturated, long acyl chains Enriched in special ‘microdomains’ of membranes Glycolipids (such as gangliosides) are abundant in specialize cell types and often carry a negative charge Pollard, et al., Cell Biology, 3rd Ed., Fig. 13.3 Cholesterol Very rigid molecule Intercalates between lipids OH-group is polar Enriched in special ‘microdomains’ of membranes Pollard, et al., Cell Biology, 3rd Ed., Fig. 13.4 Lipid composition of membranes - Mass spec analyses indicate there are 100’s of different lipid types in membranes Why??? - ensure a stable structure under changing environmental conditions - diversity of function - better ‘fit’ with certain proteins in membrane Lipid/membrane asymmetry Lipid and proteins are NOT uniformly distributed between bilayers Lipid asymmetry established by diffusion (uncatalyzed/flippase) Protein asymmetry largely established during protein biogenesis Robbins and Cotran, 9th Ed., Fig. 1-6 Lipid distribution Molecular Cell Biology, 5th Ed. Lipid distribution Pollard, et al., Cell Biology, 3rd Ed., Fig. 21.3  TOPIC: Cell Membranes LESSONS: Overview of Cells Overview of Membranes Lipid Molecules Membrane Dynamics Membrane Proteins and Membrane Transport Learning Outcomes 1. Describe the key elements of the fluid-mosaic model for membranes 2. Describe the factors that impact the fluidity of membranes 3. Describe the features of membrane rafts and their roles in cells 4. Explain the general pathway of lipid biogenesis and how asymmetry is established Lipid properties and membrane dynamics ‘Natural tendency’ of lipids to form certain structures - lipid shape favors bilayer formation - bilayers, by nature, form vesicles (micelle) - very stable structures = good and ‘bad’ Molecular Biology of the Cell, 5th Ed. Fluid-mosaic model Membranes are stable, yet fluid ‘Mosaic’ of many proteins and lipids Singer & Nicholson, 1972 Robbins and Cotran, 9th Ed., Fig. 1-6 Fluid-mosaic model - study Molecular Biology of the Cell, 5th Ed. Factors affecting fluidity 1. Temperature Molecular Cell Biology, 5th Ed. 2. Interactions of proteins and lipids with: - cytoskeleton - extracellular matrix - tight junctions Robbins and Cotran, 9th Ed., Fig. 1-5 Factors affecting fluidity 3. Lipid structure - length of acyl chain; longer = more rigid - extent of acyl chain saturation; saturated = more rigid - nature of polar head group - accommodates bending Molecular Biology of the Cell, 5th Ed. Molecular Cell Biology, 5th Ed. Factors affecting fluidity 4. Lipid composition - amount of cholesterol and sphingolipids - both alter membrane thickness - cholesterol inhibits phase transition - sphingolipids decrease fluidity Molecular Cell Biology, 5th Ed. Factors affecting fluidity 4. Lipid composition - amount of cholesterol and sphingolipids - both alter membrane thickness - cholesterol inhibits phase transition - sphingolipids decrease fluidity Molecular Cell Biology, 5th Ed. Membrane (lipid) rafts Small ‘nano-regions’ ( 2 Ca2+ ions or 1 ATP Multipass transmembrane protein