TRI1 Week 3 Membranes PDF

Introduction to Cell Biology & Biochemistry Intracellular Compartments I: Membranes Dr. Andrea Knight  Basic Functions of Cell Membranes All cells are enclosed by a plasma membrane that forms the principal divide between the inside of the cell and the outside environment...

Introduction to Cell Biology & Biochemistry Intracellular Compartments I: Membranes Dr. Andrea Knight  Basic Functions of Cell Membranes All cells are enclosed by a plasma membrane that forms the principal divide between the inside of the cell and the outside environment Intracellular membranes form the barriers for organelles and enable compartmentalisation Compartmentalisation enables the characteristics of each organelle to be maintained so that they can perform their functions effectively without compromising other intracellular compartments Alberts et al Essential Cell Biology 5th Edition  Basic Functions of the Plasma Membrane The plasma membrane is also known as the ‘cell membrane’ and forms the principal divide between the inside of the cell and the outside environment Semi-permeable membrane that enables transportation of nutrients into cells and waste products out of cells Contains proteins (receptors) that act as sensors of external signals Provides an attachment point for the intracellular cytoskeleton and cell adhesion molecules (eukaryotes) Connected to the extracellular cell wall (plant, fungi, and bacteria)  The Lipid Bilayer All biological membranes have a common structure Lipid molecules arrange as a continuous double layer ~5nm thick Provides the basic fluid structure of membranes and serves as a relatively impermeable barrier to the passage of most water-soluble molecules Structure of the lipid bilayer is attributable to the properties of the lipids (structure determines function) Alberts et al Essential Cell Biology 5th Edition  Phospholipids Phospholipids are the most abundant lipids Choline in cell membranes Phosphatidylcholine is the most abundant phospholipid in cell membranes Amphipathic molecules: Hydrophilic head group Hydrophobic tails Spontaneously form bilayers in water due to hydrophobic and hydrophilic forces Head group: glycerol, phosphate and functional group (eg. choline) Tails: fatty acids, can either be saturated, or unsaturated  Lipids Form Bilayers in Aqueous Environments Lipids spontaneously form bilayers in aqueous environments due to hydrophobic and hydrophilic interactions Planar phospholipid bilayers are energetically unfavourable due to exposed edges Lipid bilayers therefore close in on themselves to avoid exposed edges, thereby forming a sealed compartment Sealed compartment is more energetically favourable Alberts et al Essential Cell Biology 5th Edition  A Two-dimensional Fluid Individual lipid molecules diffuse freely within lipid bilayers They can flex their hydrocarbon tails, rotate within the membrane, and diffuse laterally across the membrane Individual phospholipid molecules are normally confined to their own monolayer, as such flip-flop of individual lipid molecules between monolayers very rarely occurs Composition of unsaturated and saturated fatty acids in the lipids also contributes to membrane fluidity Alberts et al Essential Cell Biology 5th Edition Discussion Question: Why are both saturated and unsaturated fatty acids important for the physiological function of biological membranes? Multiple Choice Question: Which of the following is the correct definition of ‘amphipathic’? a) A molecule that has hydrophilic properties b) A molecule that has hydrophilic properties c) A molecule that has both hydrophilic and hydrophobic properties d) A polar molecule  Other Membrane Lipids All lipid molecules in cell membranes are amphiphilic Hydrophilic head Hydrophobic tails Other major membrane lipids: Phosphatidylserine Phosphatidylethanolamine Sphingomyelin Glycolipids Cholesterol Membrane lipid composition varies for prokaryotes and eukaryotes Membrane lipid composition varies for cell membranes and organelle membranes Alberts et al Essential Cell Biology 5th Edition  Cholesterol & Membrane Fluidity Alberts et al Essential Cell Biology 5th Edition smart-biology.com Cholesterol plays an important role in the fluidity of animal cell membranes The steroid ring structure enables cholesterol to fill the space between unsaturated and saturated fatty acids of neighbouring lipid molecules Fatty acid tails proximal to polar head are more rigid  Asymmetry of the Plasma Membrane Phosphatidylcholine Sphingomyelin Glycolipids Cholesterol Phosphatidylethanolamine Cholesterol Phosphatidylinositol Phosphatidylserine Alberts et al Essential Cell Biology 5th Edition Lipid composition of the monolayers that comprise membrane bilayers is very different Glycolipids are found exclusively in the outer leaflet (cell-cell adhesion) Phosphatidylcholine and sphingomyelin are concentrated on the outer leaflet Phosphatidylethanolamine, phosphatidylserine are concentrated on the inner leaflet Phosphatidylinositol is found exclusively on the inner leaflet (signalling molecule)  Glycolipids Glycolipids Alberts et al Essential Cell Biology 5th Edition Found in the outer leaflet of cell membranes Function: Structural role to maintain membrane stability Can act as receptors for cell-cell communication Can act as anchors for peripheral membrane proteins Can act as regulators of signal transduction  Phosphatidylcholine & Sphingomyelin Phosphatidylcholine Sphingomyelin Alberts et al Essential Cell Biology 5th Edition Found in the outer leaflet of cell membranes Sphingomyelin function: Tend to be more saturated than other phospholipids Can form enriched microdomains with cholesterol Phosphatidylcholine function: One of the most abundant phospholipids in animal cell membranes Important in energy metabolism as well as structural function of cell membranes  Phosphatidylserine & Phosphatidylethanolamine Phosphatidylserine Phosphatidylethanolamine Alberts et al Essential Cell Biology 5th Edition Found in the inner leaflet of cell membranes Phosphatidylserine function: Externalised to outer leaflet during apoptosis Acts as an ‘eat me’ signal for phagocytic cells Phosphatidylethanolamine function: Regulates membrane curvature Role in membrane fusion and disassembly of the contractile ring during cytokinesis in cell division Multiple Choice Question: Which of the following best describes the following molecules: phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol? a) They are all lipids that are present in the inner leaflet of the cell membrane b) They are all lipids that have essential roles in the functioning of membranes c) They are all phospholipids that have essential roles in the functioning of membranes d) They are all phospholipids that are present in the outer leaflet of the cell membrane  Lipid rafts smart-biology.com DOI: 10.3389/fmicb.2021.631274 Small dynamic sub-domains of membranes Enriched with cholesterol, sphingolipids, and receptor proteins Lipid rafts influence: Trafficking of membrane proteins Membrane fluidity Assembly and concentration of signalling molecules Virus entry to cells  Membrane Proteins smart-biology.com Alberts et al Essential Cell Biology 5th Edition Perform most of the membrane’s specific tasks Transporters and channels Extracellular matrix and cytoplasmic anchors Receptors for extracellular signals Enzymatic activity Protein Association with Lipid Bilayers Single alpha helix Beta-barrel pore Multiple alpha helix Alberts et al Essential Cell Biology 5th Edition  7 Types of Integral Membrane Proteins 5. Interaction by hydrophobic loop 2. Multiple 7. Ionic/electrostatic transmembrane ⍺-helix interactions with membrane lipids 4. In-plane 6. Interaction by membrane helix covalently bound 3. β-barrel pore membrane lipid 1. Single transmembrane ⍺-helix  Integral Membrane Proteins Most transmembrane proteins cross the lipid bilayer in an alpha-helix Alpha-helix contains mostly non-polar (hydrophobic) amino acids held in helical shape by hydrogen bonds Single-pass transmembrane proteins cross the membrane only once Multi-pass transmembrane proteins cross the membrane multiple times Other transmembrane proteins cross the lipid bilayer by forming channels or pores. These are formed by a series of beta-sheets rolled into a cylinder called a beta- barrel The amino acid side-chains that face the outside of the barrel are hydrophobic and interact with the fatty acid tails of the lipid bilayer The amino acid side-chains that face the inside of the barrel are hydrophilic and form an aqueous channel Alberts et al Essential Cell Biology 5th Edition  Integral Membrane Proteins Some membrane proteins associate with only one leaflet of the lipid bilayer Interaction by amphipathic alpha- helix in parallel with the membrane Interaction by lipids covalently plane linked to the protein that then embed in the membrane Can act as anchors for the Can act as signalling molecules cytoskeleton for transduction of intracellular Can have enzymatic activity signalling Some are involved in protein Also involved in protein targeting processing in the ER and Golgi to various intracellular compartments Some are involved in cholesterol biosynthesis Peripheral Membrane Proteins Some proteins are indirectly associated with membranes through interactions with integral proteins Other peripheral membrane proteins may interact with membranes through: Electrostatic interactions Hydrophobic interactions Non-covalent interactions Peripheral membrane proteins can have a range of different functions: Anchoring to extracellular/intracellular structures Cell signalling Enzymatic functions Peripheral membrane proteins dissociate from the membrane following treatment with a polar reagent, or elevated pH or high salt concentrations Discussion Question: A researcher wants to investigate whether a membrane protein is integral or peripheral. How could they do this?  Not Just the Plasma Membrane The collective term given to the membranes associated with the following organelles: Nuclear Membrane Endoplasmic Reticulum Smooth Rough Golgi Apparatus Vesicle Lysosome Plasma Membrane Exocytic Vesicle Endocytic Vesicle macmillanhighered.com  Learning Outcomes Describe how the properties of lipids determine the structure and function of membranes Discuss the concept of compartmentalisation and how this is essential to cell function and specification Discuss the role of proteins in membranes