Schedule 1. The Plasma Membrane, the Lipid Bilayer ❖ Chemical structure of cell membranes ❖ Membrane proteins 2. Principles of Membrane Transport ❖ Transporters, passive and active membrane transport ❖ Ion channels and the electrical properties of membranes Schedule of the present lecture 1. The Plasma Membrane, the Lipid Bilayer ❖ Chemical structure of cell membranes ❖ Membrane proteins 2. Principles of Membrane Transport ❖ Transporters, passive and active membrane transport ❖ Ion channels and the electrical properties of membranes 1. Plasma Membrane, Lipid Bilayer Cell membranes are crucial to the life of the cell The plasma membrane ❖ encloses the cell ❖ defines its boundaries ❖ maintains the essential differences between cytosol and extracellular environment ❖ Encloses organelles inside eukaryotic cells: endoplasmic reticulum, Golgi apparatus, mitochondria … Chemical Structure of Cell Membranes Cell structures with the membrane ❖ Cytoplasmic membrane ❖ Nucleus membrane ❖ Membrane of endoplasmatic reticulum ❖ Membrane of Golgiho complex ❖ Mitochondrion ❖ Chloroplast, chromoplasts, and leukoplasts ❖ Lysozomes and spherosomes ❖ Peroxisomes and glyoxisomes ❖ Vacuoles ❖ in ATP (adenosin triphosphate) synthesis ❖ in the transmembrane transport of small molecules ❖ in cell signalling and cell adhesion ❖ protein traffic in cell compartments The role of the cell membranes The plasma membrane is ❖ very thin film of lipid (fatty) and protein molecules ❖ these molecules are hold together by noncovalent interactions Despite of their different functions, all biological membranes have a common general structure Cell membranes are dynamic, fluid structures. Most of their molecules move about in the plane of the membrane. The lipid molecules are arranged as a continuous double layer Cell membranes are dynamic, fluid structures. Most of their molecules move about in the plane of the membrane. Protein molecules span the lipid bilayer and serve structural links through the lipid bilayer to the extracellular environment or an adjacent cell. The lipid bilayer constitute the basic structure of all cell membranes Lipid molecules constitute about 50 % of the mass of the cell membranes Lipid molecules in cell membranes are amphiphilic = = they have: ❖ hydrophilic (polar) end (“water-loving“) ❖ hydrophobic (nonpolar) end (“water-fearing“) Picture : The parts of phosphoglyceride molecule Phospholipids are the most abundant membrane lipids HYDROPHILIC (POLAR) HEAD GROUP TWO HYDROPHOBIC (NONPOLAR) TAILS The tails are usually fatty acids They can differ in lengthy One tail has one or more cis double bonds …creates a small kink in the tail Picture : The parts of phosphoglyceride molecule Each Differences in the length and saturation of the fatty acid tails influence how phospholipid molecules pack against one another thereby affecting the fluidity of the membrane. The double bonds make it more difficult to pack the chains together, thereby making the lipid bilayer more difficult to freeze. The influence of cis-double bonds in hydrocarbon chains In addition, because the hydrocarbon chains of unsaturated lipids are more spread apart, lipid bilayer containing them are thinner than bilayers formed exclusively from saturated lipids. The lipid layers in many cell membranes contain: Phosphatidyl - ethanolamine - serine - choline❖ Phospholipids phosphoglycerides (they have glycerol) sphingomyeline (it have sphingosine) ❖ Cholesterol ❖ Glycolipids galactocerebrosides gangliosides PHOSPHATE GLYCEROL Ethanolamine Serine Choline Chemical Structure of Three Groups of Phosphoglycerides: 1. Phosphatidyl-ethanolamine 2. Phosphatidyl-serine 3. Phosphatidyl-choline ❖ Phospholipids SPHINGOSINE PHOSPHATE Choline Chemical Structure of Sphingomyelins ❖ Phospholipids Eukaryotic plasma membranes contain large amounts of cholesterol. Cholesterol is sterol. ..to which is attached a single polar hydroxyl group and a short non polar hydrocarbon chain It contains a rigid ring structure… ❖ Cholesterol Cholesterol molecule interacts with two phospholipid molecules in one monolayer of a lipid bilayer ❖ Cholesterol ❖ Lipid molecules which contain sugar are called glycolipids. ❖ Glycolipids are found on the surface of all plasma membranes. They have the most extreme asymmetry in their membrane distribution. ❖ They generally constitute about 5% of the lipid molecules in the outer monolayer. They are also found in some intracellular membranes. ❖ In the plasma membrane of nerve cells have been identified more than 40 different gangliosides. ❖ Glycolipids Chemical Structure of Glycolipid molecules 1. Galactocerebrosides contain sugar galactose. They are neutral glycolipid (uncharged) 2. Gangliosides contain oligosaccharides as sugar and sialic acid residues (one or more) which give gangliosides negative charge (-). ❖ Glycolipids Different cell membranes contains various types of lipids Red circle mark the largely represented type of lipid in given type of cell membrane. The lipid composition of the two monolayers of the lipid bilayer are strikingly different. phosphatidyl- serine phosphatidyl- choline phosphatidyl- ethanolamine sphingomyelin glycolipids Cholesterol (not shown) is distributed roughly equally in both monolayers phosphatidyl- choline sphingomyelin phosphatidyl- ethanolamine phosphatidyl- serine Asymmetry of the Lipid Bilayer OUTER MONOLAYER (touch extracellular space) Almost all of the phospholipid molecules contain CHOLINE chain in their molecules (= phospatidyl-choline + sphingomyeline) INNER MONOLAYER (touch cytosol) Almost all of the phospholipid molecules contain terminal primary amino group in their molecules (= phosphatidyl-ethanolamin + The inner monolayer is negative charged, but outer monolayer is neutral has negative charge Asymmetry of the Lipid Bilayer phosphatidyl-serin) Asymmetry of the Lipid Bilayer Lipid asymmetry is functionally important especially in signaling pathways (converting extracellular signals into intracellular signals). On the cytosolic face of the plasma membrane (inner monolayer) are ❖ specific proteins proteinkinase C (PKC), phospholipase C ❖ specific lipid head groups phosphatidylinositol ❖ specific lipid kinases phosphoinositide 3-kinase (PI3- kinase) Membrane Proteins Each type of cell membrane have characteristic functional properties The membrane's specific tasks perform proteins in cell membrane, therefore there are various types of proteins The amount of proteins in cell membrane differ ❖ in myelin membrane proteins consist less than 27% of the membrane mass ❖ in membranes of mitochondria a total of 75 % of the mass are proteins ❖ Transmembrane proteins They extend through the lipid bilayer On either side is the part of their mass ❖Proteins located entirely in the one side of membrane Proteins are anchored in the internal or external side of membrane Membrane proteins are They are amphiphilic, having hydrophobic and hydrophilic regions pass through the membrane and interact with the hydrophobic tails of the lipid molecules in the bilayer are exposed to water on either side of the membrane ❖ Transmembrane proteins This picture shows the different ways in which the membrane proteins can associate with the membrane  Most transmembrane proteins are throught to extend across the bilayer as single α helix = single-pass transmembrane proteins some of these proteins are covalently attached to fatty acid chain inserted in cytosolic monolayer This picture shows the different ways in which the membrane proteins can associate with the membrane  …or as multiple α helices = multipass transmembrane proteins This picture shows the different ways in which the membrane proteins can associate with the membrane  Other transmembrane proteins extend across the bilayer as a rolled–up β sheet (β barrel) ❖Proteins located entirely in the one side of membrane (internal or external side). They are attached to the lipid chain, phosphaditylinositole group of phospholipids or to the other transmembrane protein. Sometimes these proteins (enzymes, signaling proteins) are anchored by GPI (glyco phosphatidyl-inositol) anchor into correct place of cytosolic side of the membrane. This picture shows the different ways in which the membrane proteins can associate with the membrane  Other membrane proteins exposed at only one side of the membrane - some of these are anchored to the cytosolic surface by an amphiphilic α helix This picture shows the different ways in which the membrane proteins can associate with the membrane  Others are attached to the bilayer only (specifically) by a covalent bond with lipid chain or fatty acid chain or a prenyl group or via a oligosaccharide linker to PI (phosphatidylinositol) – called GPI (glyco-PI) anchor  This picture shows the different ways in which the membrane proteins can associate with the membrane   Many proteins are attached to the membrane only by noncovalent interactions with other membrane proteins ❖ Functions of membrane proteins ❖ Cell surface receptors (e.g. GPCR = G protein coupled receptors) Transmembrane proteins can functions as The signal molecule in the extracellular side binds on the extracellular part of receptor protein. This binding generate intracellular signal on the opposite side of the plasma membrane. ❖ Functions of membrane proteins ❖ Transporters (carriers or permeases) Transmembrane proteins Transporters bind the specific solute and undergo a series of conformational changes to transfer the bound solute across the membrane. ❖ Functions of membrane proteins ❖ Channels (inorganic ions) Transmembrane proteins Channel proteins form a water-filled pore across the bilayer through which specific inorganic ions can diffuse. ❖ Functions of membrane proteins ❖ Intracellular signalling molecules (proteins of Src family, Ras, Raf proteins,…) ❖ Enzymes (proteinkinases, adenylylcyclases, phospholipases) Proteins, which are only on one side of the lipid bilayer These proteins are often associated exclusively with either the lipid monolayer or a protein domain on that side. Transmembrane protein always has a unique orientation in the membrane In order to membrane protein is attached to fatty acid chain or a prenyl group. The covalent attachment of certain type of lipid can help to localise a protein to a membrane after its synthesis in the cytosol. The lipid anchors are: Myristoyl anchor, Palmitoyl anchor, Farnesyl anchor A fatty acid chain (myristic acid) is attached via an amide linkage to an N-terminal glycine 1) Myristoyl anchor 2) Palmitoyl anchor A fatty acid chain (palmitic acid) is attached via a thioester linkage to a cysteine 3) Farnesyl anchor A prenyl group (either farnesyl or longer geranylgeranyl group) is attached via a thioether linkage to a cysteine residue Many of the membrane proteins are glycosylated Because most trans membrane proteins in animal cells are glycosylated*, carbohydrates extensively coat the surface of all eukaryotic cells. *The sugar residues are added in the lumen of the ER and the Golgi apparatus. 1. The Plasma Membrane, the Lipid Bilayer Summary Biological membranes consist of a continuous double layer of lipid molecules in which membrane proteins are embedded The lipid bilayer is fluid – The membrane lipid molecules are amphiphilic and they are able to diffuse rapidly within their own monolayer. Cells contain 500-1000 different lipid species – there are three major classes of membrane lipids – phospholipids, cholesterol and glycolipids. The lipid composition of the inner and outer monolayers a different, reflecting the different functions. Plasma membrane lipid bilayer play an important part in cell signalling (see lecture Principles of cell communication – signaling pathways) 1. The Plasma Membrane, the Lipid Bilayer Summary