Eukaryotic Cell Membrane Lecture Notes PDF

SBP3411 Eukaryotic Cell Membrane Dr. Hanis H. Harith Dept. of Biomedical Science, UPM [email protected]  Learning Outcomes At the end of this lecture the student is able to: Describe the composition and properties of eukaryotic cell membrane Explain how membrane lipids...

SBP3411 Eukaryotic Cell Membrane Dr. Hanis H. Harith Dept. of Biomedical Science, UPM [email protected]  Learning Outcomes At the end of this lecture the student is able to: Describe the composition and properties of eukaryotic cell membrane Explain how membrane lipids and proteins influence the properties of cell membrane Describe the importance of cell membrane properties in cell biology Discuss the importance of membrane proteins in specialized function of cell membrane Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Lecture Outline Membrane structure Membrane properties Membrane assembly Membrane proteins Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM  Eukaryotic cell membrane A selective barrier that prevents mixing of contents from different sides Plasma membrane vs internal membrane: Ø Similar structure Ø Individual characteristics/functions are largely determined by composition of membrane proteins Eg. Receptors for cell signalling Eg. Cell movement or division Eg. Cell metabolism Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM The composition of cell membrane Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Composed of: Ø ~50% lipid molecules Ø Proteins Membrane lipids Ø amphiphilic Ø form bilayers spontaneously in an aqueous environment Membrane lipids Phospholipids Glycolipids Sterols Phosphoglycerides Sphingolipids Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Phospholipids: The major type of membrane lipids Several types which depends on the backbone or polar head group Phosphoglycerides: Ø Glycerol backbone Ø Most abundant in mammalian cells: phosphatidylcholine, Essential Cell Biology, Fifth Edition phosphatidylserine, Copyright © 2019 W. W. Norton & Company phosphatidylethanolamine Alberts et al. (2015). Molecular Biology of The Cell (6th Edition) Sphingolipids: Ø Sphingosine backbone Ø Most common in mammalian cells: sphingomyelin Hanis Harith SBP3411 (2020) Dept of Biomedical Science UPM The flexibility of the lipid bilayer Spontaneously forms a sealed compartment in aqueous environment Ø e.g. vesicles, organelles, cells Self-healing/self-sealing Ø Enables repair of small tears Ø Large tears may result in separate closed vesicles most energetically favorable rearrangement Ø To eleminate free edges Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM The fluidity of the lipid bilayer Behaves as a 2D fluid; membrane lipids move about within the same layer due to random thermal motions Cholesterol’s short and rigid steroid Essential Cell Biology, Fifth Edition ring structure allows it to fill the gap Copyright © 2019 W. W. Norton & Company Membrane fluidity is influenced by its composition (at a given temperature) Ø shorter HC tails increases membrane fluidity Ø greater proportion of unsaturated HC tails (double bonds) increases membrane fluidity Ø cholesterol reduces mobility of lipids and membrane permeability Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM  The biological significance of membrane fluidity Allows appropriate Cell distribution of new expansion membrane lipids e.g. lipid asymmetry Allows even distribution Cell of membrane molecules division between daughter cells e.g membrane assembly Allows rapid diffusion Cell and interaction of signaling membrane proteins e.g. lipid raft This Photo by Unknown Author is licensed under CC BY-NC Allows membrane Membrane budding and fusion trafficking when required Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Lipid asymmetry in the plasma membrane: Biological significance Glycolipids Phosphatidylcholine Sphingomyelin Distribution of membrane lipids vary between cytosolic vs non- cytosolic monolayer (cell’s exterior or organelle’s interior space) Phosphatidylserine Phosphatidylinositols Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Phosphatidylethanolamine Highly distributed in the non-cytosolic layer: Ø Glycolipids: sugar groups attached form glycocalyx that protects the cell Highly distributed in the cytosolic layer: Ø Phosphatidylserine (negatively charged head): § Important for the recruitment & activity of some enzymes involved in signal transduction § Used as an indicator for apoptotic cells: translocated to the noncytosolic layer Ø Phosphatidylinositol: § Its modification by lipid kinases (eg. PI3K) is important for the recruitment of signaling proteins § Its cleavage by phospholipases (eg. PLC) to generate short-lived intracellular signaling mediators Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Membrane assembly and lipid asymmetry Vesicles pinch off from the Golgi Phospholipids are synthesized Some pinch off the ER to supply apparatus to fuse with the using FFA by enzymes bound to fresh membrane to other plasma membrane the cytosolic surface of ER intracellular compartments Non-cytosolic Cytosolic Lipid asymmetry is preserved as membranes bud from one location to another Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Glycolipids and glycoproteins form glycocalyx Alberts et al. (2014). Essential Cell Biology (4th Edition) Glycocalyx is a carbohydrate layer that surrounds eukaryotic cells Ø Protects cells from ionic stress, mechanical stress & invading microorganisms Ø Gives slimy surface which facilitate cell motility and prevents unnecessary cell adhesion Ø Cell-type specific: Plays a role in specific cell-cell interaction Made up of oligosaccharide chains covalently attached to lipid molecules (glycolipids) or membrane proteins (glycoproteins) and polysaccharide chains attached to proteoglycans (a group of membrane proteins with one or more long polysaccharide chains) Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Membrane proteins carry out membrane function Alberts et al. (2014). Essential Cell Biology (4th Edition) Specialized function of a particular membrane is determined by the set of membrane proteins it contains Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Integral and peripheral membrane proteins E.g. GPI-anchored proteins E.g. receptors or enzymes E.g. intracellular signaling proteins Alberts et al. (2014). Essential Cell Biology (4th Edition) The types of association to the cell membrane facilitate their function Understanding the specialized function of a membrane requires isolation of membrane proteins while retaining their structure Peripheral membrane proteins: Gentle extraction methods (to disrupt the non- covalent interactions between proteins) Integral membrane proteins: Can be solubilized in detergents (agents that destroy the lipid bilayer by disrupting the hydrophobic associations) Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Orientation of transmembrane proteins in the lipid bilayer Single/multipass ⍺ helix maximizes hydrogen (amphipathic) bonds interaction between the polar peptide bonds (hydrophilic) aa with hydrophobic side chains interact with hydrophobic lipid Modified from Alberts et al. (2014). Essential Cell Biology (4th Edition) tails Adapted from Essential Cell Biology (6th Edition) Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Membrane protein diffusion can be restricted Membrane proteins can rotate (rotational diffusion) and move laterally (lateral diffusion) Membrane proteins can be immobilized: Ø Attachment to structures outside/inside the cell, surface molecules of adjacent cells Alberts et al. (2014). Essential Cell Biology (4th Edition) Cell cortex ECM Biological significance: Ø Reinforcement of plasma membrane (stabilized by a meshwork of filamentous intracellular proteins linked to Apical membrane proteins) e.g. Tight junction Ø Regulation of morphological changes or motility Ø Formation of functionally specialized region (membrane domains) on the cell or organelle surface Basal Ø Formation of barriers to restrict membrane components Eg. Epithelial cells to one domain eg. cell polarity Modified from Alberts et al. (2014). Essential Cell Biology (4th Edition) Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM Lipid rafts Transiently formed, relatively ordered membrane domains: Ø Usually enriched in cholesterol, sphingolipids, glycolipids, GPI-anchored proteins and transmembrane proteins Ø facilitated by weak protein-protein, protein-lipid and lipid-lipid interactions Alberts et al. (2015). The Molecular Biology of the Cell (6th Edition) Ø Increased lipid packing and order, decreased fluidity Ø Membrane proteins interact with cytoskeleton (actin) Membrane proteins are organized into clusters for certain processes eg. vesicle transport, signal transduction Hanis Harith SBP3411 (2023) Dept of Biomedical Science UPM References Alberts, B., Bray, D., Hopkin, K., Johnson, A., Lewis, J., Raff, M., Roberts, K. & Walter, P. (2019). Essential Cell Biology (5th Edition). New York: W.W. Norton & Company. Alberts, B., Bray, D., Hopkin, K., Johnson, A., Lewis, J., Raff, M., Roberts, K. & Walter, P. (2014). Essential Cell Biology (4th Edition). New York: Garland Science, Taylor & Francis Group. Alberts, B., Johnson, A., Lewis, J., Morgan, D., Raff, M., Roberts, K. & Walter, P. (2015). Molecular Biology of The Cell (6th Edition). New York: Garland Science, Taylor & Francis Group Cooper, G.M. & Hausman, R.E. (2016). The Cell: A Molecular Approach (7th Edition). Massachusetts: Sinauer Associates, Inc. Sezgin, E., Levental, I., Mayor, S., & Eggeling, C. (2017). The mystery of membrane organization: composition, regulation and physiological relevance of lipid rafts. Nature Reviews. Molecular Cell Biology, 18(6), 361–374. http://doi.org/10.1038/nrm.2017.16