Berg Tymoczko Stryer Biochemistry Seventh Edition Chapter 12 Lipids and cell membrane Section 12 1 12 3 Lipids and bilayers Copyright 2012 by W H Freeman and Company Concepts cid 190 Membranes are sheet like structures Self assemble Lipids proteins and carbohydrates Amphipathic lipids cid 190 3 classes of lipids Phospholipids Sphingolipids Cholesterol cid 190 Lipid assembly in sheets and liposomes cid 190 Membranes are barrier to diffusion Cell membranes Non covalent assembly of proteins and lipids that form self sealing sheet like structures bilayer Essentially components of cells and organelles compartmentalize processes Fluid 2D diffusion of lipids and proteins Hydrophobic environment Asymmetric organization Have distinctive function related to composition and position in cells Key components Lipids Proteins Carbohydrates Courtesy of A Kusumi 6 10 nm Lipids Fatty acids Lipids are primary components of membranes Lipids are amphipathic molecules Apolar tail hydrophobic Polar head hydrophilic Fatty acids are key components of lipids long hydrocarbon chains 14 24 C with carboxyl group Palmitate C16 Oleic acid C18 16 0 16C no double bound 18 1 18C with 1 double bound Saturated fatty acid Unsaturated fatty acid lower melting point Lipids Fatty acids Nomenclature Numbering starts from carboxyl group Last methyl carbon called omega carbon If double bond the end of the systematic name changes from anoate to enoate Position of a double bond represented by a delta A double bond can be cis or trans Lipids Fatty acids Examples using nomenclature Palmitic acid 10 9 n Hexadecanoate C16 16 H3C cis 9 Octadecenoate C18 18 18 Trans 9 Octadecenoate C18 10 9 1 1 1 Unsaturation and short length fatty acids lower melting temperature more fluidity 3 classes of membrane lipids 1 Phospholipids Phosphatidylserine Sphingomyelin 3 classes of membrane lipids 1 Phospholipids Common alcohol groups for phosphoglycerides 3 classes of membrane lipids 2 Glycolipids Glycolipids can have many carbohydrate residues Glycolipids are oriented asymmetrically in the plasma membrane and are always facing the extracellular side 3 classes of membrane lipids 3 Cholesterol A steroid made from Oriented parallel to other lipids OH interacts with phospholipid heads Mainly in plasma membrane four carbon rings one hydroxyl group one alkyl chain Amphipathic properties of lipids Apolar tail hydrophobic Polar head hydrophilic Effects of the amphipathic nature of membrane lipids Preferential arrangement in micelles or bilayers to bury hydrophobic fatty acids tails Single fatty acid chain formation of a micelle Two fatty acid chains formation of a bilayer curving closing Liposome Self assembly process driven by hydrophobic interactions between fatty acid chains Close packing is directed by van der Waals interactions between hydrocarbon chains Liposomes as nanocontainers and nanoreactors Liposome can be used as nanocontainers Liposome can be used as nanoreactors e g Synthesis of calcium carbonate nanoparticles e g Thermodox Liposomal doxorubicin Target cancer tissue Apply radio frequency wave Heat releases dox Clinical trials For liver and breast cancers Tester et al CrystEngComm 2011 13 3975 3978 Lipid bilayers are barriers to diffusion Low permeability to ions need desolvation to go through the membrane directly Low permeability to polar molecules except H2O small and uncharged Highly selective permeability barriers to ions using proteins pump and channels Maintain different ion conc on each side of the membrane membrane potential of 60 mV Low permeability of Na due to unfavorable desolvation energetics And to other ion is responsible for electrical polarization of cell across the plasma membrnae 60 mV Review of concepts cid 190 Membranes are sheet like structures Self assemble Lipids proteins and carbohydrates Amphipathic lipids cid 190 3 classes of lipids Phospholipids Sphingolipids Cholesterol cid 190 Lipid assembly in sheets and liposomes cid 190 Membranes are barrier to diffusion Berg Tymoczko Stryer Biochemistry Seventh Edition Chapter 12 Lipids and cell membrane Section 12 4 12 6 Membrane proteins dynamics Copyright 2012 by W H Freeman and Company Concepts cid 190 Membranes are rich in proteins Integral proteins Peripheral proteins cid 190 Various approaches to attaching proteins to membranes cid 190 Membranes are dynamic and asymmetric Membrane spanning helices sheets Partial embedding Direct lipid anchoring Fluidity and lipid composition Temperature Cholesterol Flippase Proteins are key components of membranes Lipids provide barrier and proteins provide most functions of membranes Membrane proteins involved in Transports across membranes Signaling and transfer of information Maintenance of electric potential Depending on membranes lipid proteins ratio varies from 1 4 to 4 1 Large variations in protein repertoire between different membranes Type of membrane proteins is related to membrane function Gel electrophoresis of protein content in A Erythrocyte membrane ABO group HCO3 exchange B Retinal rod cells photoreception C Sarcoplasmic reticulum of muscle cells Ca2 storage and release Multiple types of protein association with membranes 3 major types of membrane anchoring Transmembrane very strong association Electrostatic interaction weak Lipid anchoring strong association Membrane spanning integral proteins Membrane bound peripheral proteins Mechanistic of protein membrane interactions Integral membrane proteins use different strategies to accommodate the polar peptide backbone across the hydrophobic membrane core Alpha helices very common 7 span proteins e g G coupled receptors 20 aa helix Extensive H bonding helices are formed of hydrophobic aa residues 1 helix 3 6 aa turn 1 turn 0 54 nm Bilayer core 3 nm aa helix 20 Bacteriorhodopsin Mechanistic of protein membrane interactions Strategies to accommodate polar peptide backbone across the hydrophobic membrane core Alpha helices continued One can predict transmembrane domains from primary sequence of proteins 1 2 3 4 5 6 7 Hydropathic index here 7 aa sliding window Uses G of aa when transferred from an hydrophobic to an aqueous environment Kyte and Doolitlle J Mol Biol 1982 157 105 132 Mechanistic of protein membrane interactions continued Calculating an hydropathic index Free energy of transfer of aa from membrane to water glycophorin helix Criterion level Sliding window of 20 aa Criterion level of 84 Mechanistic of protein membrane interactions continued Strategies to