CELLULAR MEMBRANES Plasma Membrane Thin and fragile 5 to 10 nm wide J.D. Robertson The plasma membrane is a trilaminar layer Trilaminar layer: Dark staining inner and outer layer, lightly staining middle layer Membrane has a lipid bilayer: Polar surface (polar head) and non-polar tails Membrane Functions 1. Compartmentalization Membranes are continuous and unbroken sheets Function: enclose compartments in the cell (the nuclear and cytoplasmic membranes enclose intercellular spaces) The compartments allow specialized activities to proceed without any external interference and there is regulation of the cellular activities 2. Scaffold for biochemical activities Membranes are also scaffolds
As long as there are reactants present in the solute, relative position cannot be stabilized Interactions in the cell depend on random collisions Function: Membranes provide the extensive framework of scaffolding which components can be ordered for effective interaction
3. Providing a selectively permeable barrier Provide a barrier that prevents the unrestricted exchange of molecules from one side to another Function: For communication between compartments as it separates Function: Promote movement of selected elements into and out of the enclosed living space 4. Transporting solutes Transports substances from one side to another side Follows the pathway of lower concentration to higher concentration There will be an accumulation of sugar and amino acids for
metabolism and macromolecules Transport ions- ionic gradient (nerve and muscle cells)
5. Responding to external stimuli Response of a cell to the external stimuli Signal transduction: receptors bind to ligands Respond to other types of stimuli such as light or mechanical tension Signals generated may stimulate or inhibit internal activities Ex: 1. Signals generated at the plasma membrane may tell a cell to manufacture more glycogen 2. Prepare for cell division 3. Move toward a higher concentration of a particular compounds 4. Release calcium from internal stores 5. Commit suicide (apoptosis) 6. Intercellular interaction Interaction of a cell with its neighbors Outer edge of the living plasma membrane 1. Cells can recognize one another
2. Adhere to one another (cell adhesion) 3. Exchange materials and information Proteins can facilitate interaction between extracellular materials and intracellular cytoskeleton 7. Energy transduction Energy is converted from one type to another type Photosynthesis has the most abundant energy transduction (light energy to chemical energy) Energy from the sun is absorbed by the membrane bound pigments (energy will be stored as carbohydrates) Plasma Membrane Structure Ernst Overton - Lipids are chemical in nature - Like dissolves like (non-polar solute dissolves in nonpolar solvent) - Used plant root hairs: more lipidsoluble the solute, more rapidly it would enter the root hair cells
E. Gorter and F. Grendel - Cellular membranes have a lipid bilayer - Extracted lipid from red blood cells and measured the amount of surface area the lipid would cover when spread over the surface of water - Ratio of surface area of water covered by extracted lipid 2:1 - Polar groups of molecular layers or leaflets were directed outwards towards the aqueous environment
Hugh Davson and James Danielli - Cellular membranes were not purely made up of a lipid bilayer - Surface tension can lower the pure lipid structure - Plasma membrane was composed of a lipid bilayer that as lined on both its inner and outer surface by globular proteins - Protein-lined pores - WRONG MODEL
Jonathan Singer and Garth Nicolson - FLUID-MOSAIC MODEL - Bilayer of a fluidmosaic model is in a fluid state - Lipid molecules move laterally in the plane of the membrane - “Mosaic” – of discontinuous particles that penetrate the lipid sheet (Made up of lipids and proteins) - The cell membrane is DYNAMIC - Proteins penetrate the lipid bilayer o Peripheral Proteins o Integral Proteins
Chemical Composition of Membranes Membrane Lipids Membranes are made up of Lipids and proteins Held together by noncovalent bonds Ratio of lipid to protein in membrane varies and depends on the type of cell membrane (plasma or endoplasmic reticulum or Golgi), type of organism (bacterium, animal or plant), type of
cell (cartilage, muscle or liver) Ex: The inner mitochondrial membrane has a high ratio of protein/lipid in comparison to the red blood cell plasma membrane - The myelin sheath acts as a primarily as electrical insulation for the nerve cell it encloses Membranes are amphipathic – can be hydrophilic or hydrophobic 1. Sphingolipids 2. Phospholipds 3. Cholesterol
Phosphoglycerides Contain a phosphate group Glycerol backbone: Phosphoglycerides Diglycerides: two of the hydroxyl (OH) groups of glycerol are esterified to the fatty acids and the third OH is esterified to a hydrophilic phosphate group and two fatty acyl chain – Phosphatidic acid Phosphatidylcholine (PC) Phosphatidylethanolam ine (PE) Phosphatidylserine (PS) Phosphatidylinositol (PI)
Phosphatidyl groups are small and hydrophilic and together with the negatively charged phosphate to which it is attached, forms a highly water-soluble domain at one end of the molecule: HEAD GROUP Membrane fatty acid may be saturated, monounsaturated, saturated or polyunsaturated
Sphingolipids Sphingosine backbone Sphingosine is linked to a fatty acid Ceramide If phosphorylcholine – sphingomyelin Carbohydrate: Glycolipid Simple sugar: Ceramide - sialic acid, ganglioside Nervous system is rich in glycolipid Myelin sheath: galactocerbroside Cholesterol Most of the animal cells are made up of cholesterol Plant cells contain cholesterol-like sterols Made up of 4 different rings – rings of are flat and rigid
The Nature and Importance of the Lipid Bilayer Lipid composition can determine the physical state of the membrane and influence the activity of the particular membrane proteins Membrane proteins also provide the precursors for highly active chemical messengers that regulate cellular function Lipid membrane is thought to facilitate the regulated fusion or budding of membranes Lipid bilayer maintains the proper internal composition of a cell Lipid bilayer is capable of self-assembly Ex: Liposomes The Asymmetry of Membrane Lipids Lipid digestive enzymes cannot penetrate the plasma membrane and are only able to digest lipids that reside in the outer leaflet of the bilayer Membrane Carbohydrates Plasma membranes also contain carbohydrates (sugars) More than 90 percent of the membrane’s carbohydrate is covalently linked to proteins to form glycoproteins Addition of a carbohydrate: Glycoslation Oligosaccharides
Structure and Functions of Membrane Proteins Membranes may contain many types of proteins Asymmetry is referred to as ‘sidedness’ Integral proteins Penetrate the lipid bilayer Transmembrane proteins Constitute 25-30 percent of all encoded proteins and roughly 60 percent of all current drug targets Most are receptors that bind to specific substances at the membrane surface Acts as channels, transporters involved in the movement of ions, solutes across the membrane or transfer of electrons Amphipathic Van der Waals forces “hydrophobic” seals it with the membrane Protein is anchored to the bilayer Globular proteins: These are the portions of the integral membrane protein that project into either the cytoplasm or the extracellular space – hydrophilic, low molecular weight substrates, hormones and other proteins Distribution of Integral Proteins: Freeze-Fracture Analysis Freeze fracture replication Used as a technique to investigate the cell membrane structure
“Membrane-associated particles”
Structure and Properties of Integral Membrane Proteins Integral proteins have hydrophobic transmembrane domains
Peripheral Membrane proteins Outside of the lipid bilayer Associated with the surface of the membrane with noncovalent bonds It is associated with the membrane with weak electrostatic bonds High concentration salt solutions weaken the electrostatic bonds Ex of peripheral proteins: These are located on the internal (cytosolic) surface of the plasma membrane, where they form a fibrillar network that acts as a membrane skeleton Dynamic relationship with the membranebeing recruited to the membrane
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Lipid-Anchored Membrane proteins Outside the lipid bilayer on either the extracellular or cytoplasmic surface Covalently linked to a lipid molecule that is situated within the bilayer GPI-anchored proteins These group of proteins are present on the cytoplasmic side of the plasma membrane and is anchored to the membrane by one or more long hydrocardbon chains embedded in the inner leaflet of the lipid bilayer Membrane Lipds and Membrane Fluidity Membrane Fluidity Physical state of the lipid depends on its viscosity or fluidity If temperature is warm: lipid is relatively at a fluid state (membrane is a twodimensional liquid crystal) Transition temperature: change from the liquid crystal state to the frozen crystalline gel – change in the temperature The shape of a saturated fatty acid: shape of a flexible rod Cis-unsaturated fatty acid: crooks in the chain
Importance of Membrane Fluidity Membrane fluidity provides a perfect compromise between a rigid, ordered structure Mobility can be absent and there will be fluidity Nonviscous liquid could not be oriented Fluidity is what lets interactions take place within the membrane Fluidity also allows membrane assembly Maintaining membrane fluidity Membranes of a cell should remain fluid Cells respond to changing conditions by altering the types of phospholoipids in which they are made up of Maintaining the fluidity can be 1. Changing the temperature 2. Desaturating single bonds in fatty acly chains to form double bonds (desaturates) 3. Reshuffling the chains between different phospholipid molecules (phospholipases) Liquid rafts Formation of the artificial lipid bilayer The artificlal lipid bilayer – cholesterol and sphingolipids tend to self-asemble
The patches of cholesterol and the sphinglolipids are what are termed as lipid rafts “random sea of lipid molecules’
Dynamic Nature of the Plasma Membrane Diffusion of Membrane Proteins after Cell Fusion
Control of Mobility
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Membrane Lipid Mobility
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Membrane Polarity
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Integral Proteins Erythrocyte Membrane
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Movement of Substance Across Cell Membrane Membrane Potentials and Never impulses
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