Lecture 18: Introduction to Membranes Lipid Structure Properties of Lipid Bilayers

Mitochondria Lysozome Peroxisome Golgi complex Plasma membrane Nucleus Endoplasmic Reticulum Nutrients Wastes Biological Membranes Define the Boundaries of the Cell and its Compartments Membranes are permeability barriers that keep the cell contents in and unwanted substances out. Membranes are selectively permeable: specific substances can cross membranes in a controlled way through protein-based transport systems. The various organelles and compartments of the cells are bounded by membranes to create interior environments suitable for different functions.

Common Features of Biological Membranes Membranes are sheet-like structures, 2 molecules thick, or 60 to 100 Angstroms across. Lipids and proteins are the major components of membranes, occurring in the ratio of 1:4 to 4:1. Both can be covalently modified by carbohydrates. Lipids are small molecules with both hydrophobic and hydrophilic groups. They associate to form double layers called lipid bilayers, which are impermeable to polar molecules. Proteins associated with or embedded in the lipid bilayer carry out the different functions of membranes. These proteins serve as pumps, channels, receptors, energy transducers, and enzymes. Both lipid and protein components of membranes are held together by noncovalent bonds. Membranes are asymmetric- the two layers are not equivalent. Lipids can flow and diffuse within a layer, but cannot in general cross to the other layer. Most membranes are electrically polarized, enabling transport of molecules, energy conversion, and transmission of signals.

Nonpolar “tails” Polar “head” Schematic Structure of a Membrane Lipid Schematic Structure of a Lipid Bilayer Layer 1 Layer 2

Example Functions of Membranes PERMEABILITY BARRIERS: Regulation of molecular and ionic compositions of cells and intracellular organelles a) channels & pumps (proteins that act as selective transport systems) b) electrical polarization of membrane (due to differences in ion concentrations on opposite sides) INFORMATION PROCESSING biological communication a) signal reception by specific protein receptors (BINDING) b) transmission/transduction of signals (via protein conformational changes) ENERGY CONVERSION ordered arrays of enzymes to organize of reaction sequences a) photosynthesis (conversion of light energy to provide chemical bond energy) b) oxidative phosphorylation (oxidation of fuel molecules to provide chemical bond energy)

Lipids Lipids are a diverse group of biological molecules which share the common solubility property of being insoluble in water but highly soluble in organic solvents. Lipids can serve diverse biological roles (energy sources, signalling molecules) but we will focus on membrane lipids- lipids whose primary role is as components of biological membranes. Three major types of membrane lipids: Phospholipids Glycolipids Cholesterol

Fatty Acids Fatty acids are components of phospholipids and glycolipids. They consist of long hydrocarbon chains that terminate with a carboxylic acid. Palmitate: 16 carbons (fully saturated) Oleate: 18 carbons (monounsaturated) Kink at 9 th carbon The hydrocarbons of fatty acids vary in length (16 and 18 carbons are the most common) and also in the number and position of double bonds.

Fatty Acid Nomenclature: Substitute oic for e in name of parent alkane: octadecane is an alkane with 18 carbons octadecanoic acid is the fatty acid derived from octadecane (18:0) Substitute enoic for ene in name of parent alkene: octadecene is an alkene with 18 carbons, 1 double bond octadecenoic acid is the fatty acid derived from octadecene (18:1) Fatty acids containing more than one double bond are given the suffixes -dienoic, -trienoic, etc. octadecadienoic acid has 18 carbons and 2 double bonds (18:2) octadecatrienoic acid has 18 carbons and 3 double bonds (18:3) An alkane is a hydrocarbon with no double bonds. An alkene is a hydrocarbon containing one or more double bonds. A shorthand notation to describe the degree of unsaturation: 18:0 represents a fatty acid with 18 carbons and 0 double bonds 18:1 represents a fatty acid with 18 carbons and 1 double bond 18:2 represents a fatty acid with 18 carbons and 2 double bonds… Description of Fatty Acids

The carbon atoms are numbered from the carboxyl group. The position of double bonds, and whether they are cis or trans, can be indicated by the  notation, e.g. oleate can be referred to as cis-  9 -octadecenoate (cis double bond between carbons 9 and 10) The last carbon is referred to as the  carbon. Consuming foods rich in  -3 fatty acids, such as salmon, is believed to protect against heart disease. trans cis Oleate

Phospholipids and Glycolipids Phospholipids are a major class of membrane lipids, and are comprised of a “platform” or central backbone compound (glycerol or sphingosine), fatty acids, a phosphate, and an alcohol. The presence of a phosphate group is the primary identifier. These have charged head groups. Glycerol: CH CH CH 22 OH Sphingosine: Glycolipids are another class of membrane lipids. The platform is sphingosine, with a fatty acid linked to the amino group and one or more sugars to the primary hydroxyl. These have polar head groups.

Phosphoglycerides C O O R1 O C O R2 H CH CH CH 2 O P O O O - Fatty Acids Phosphate Alcohol Glycerol Phosphate-containing lipids built from glycerol are phosphoglycerides. They contain 2 fatty acids esterified to two of the hydroxyl groups on glycerol, and the third hydroxyl is esterified to phosphoric acid. The phosphate group is typically further esterified to other alcohols. Nonpolar fatty acid tails Polar (charged) head group

The simplest phosphoglyceride is phosphatidate in which the phosphate is not esterified. Other common phosphoglycerides can be formed by addition of hydroxyl- containing groups: serine, choline, ethanolamine, inositol. (lecithin)

An example of phospholipids based on sphingosine are the sphingomyelins. The amino group of sphingosine forms an amide bond to a fatty acid and the primary hydroxyl is esterified to phosphoryl choline or phosphoryl ethanolamine. Sphingophospholipids Nonpolar tails Polar (charged) head group

Glycolipids Glycolipids are based on sphingosine and also form an amide bond with a fatty acid. The primary hydroxyl is esterified to one or more sugars. Cerebrosides have a single sugar and gangliosides have a branched chain of up to seven sugars. Glycolipids are found on the exterior layer of the plasma membrane with the sugars ouside the cell. Nonpolar tailsPolar head group

Phospholipids (charged) Phosphoglycerides (based on glycerol) Sphingophospholipids (based on sphingosine) Phosphatidyl choline Phospatidyl serine Sphingomyelins Glycolipids (based on sphingosine. uncharged) Cerebrosides Gangliosides Nonpolar tails Polar or charged head group

Cholesterol An important lipid of entirely different form is cholesterol. Its backbone is a steroid, a 4-ring structure, with a hydrocarbon tail, and a polar hydroxyl group. It is particularly abundant in some kinds of nerve cell membranes.

Lipids Spontaneously Form Bilayers In aqueous solution, the nonpolar tails of phospholipids and glycolipids tend to associate to minimize contact with water, but the polar head groups tend to seek contact with water. Two ways to satisfy both requirements are to form micelles or bilayers. Micelles are formed by fatty acids, detergents. Typically smaller than 200 Angstroms. Bilayers are formed by phospholipids. The 2 fatty acid chains are too large to fit in the interior of a micelle. Bilayers can be very large, up to 10 Angstroms (1 mm). 7

Bilayer Self-Assembly Bilayers are stabilized primarily by hydrophobic interactions between the nonpolar tails but also by Van der Waals interactions and also hydrogen bonding between the polar head groups and water. Bilayers seek to avoid exposure of the hydrophobic tails of lipids to water so can be very extensive. To avoid such exposure they form closed compartments. Any holes that form in the bilayer are energetically unfavorable so bilayers are self-sealing.

Formation of Lipid Vesicles The self-sealing property of bilayers allows creation of lipid vesicles or liposomes- small membrane-bounded compartments containing a desired substance. These vesicles have clinical uses such as drug delivery. The ability to create membranes with concentration gradients across them is useful for the study of membrane proteins.

Permeability of Bilayers Bilayers are nearly impermeable to ions and most polar molecules other than water. The rate at which such substances traverse the membrane is correlated with their solubility in nonpolar solvents. Polar or charged molecules must be desolvated (shed bound water) before they can spontaneously cross the membrane, which is unfavorable.

Summary: Biological membranes are composed of lipids and proteins and form the boundary of the cell and its compartments. Phospholipids and glycolipids are formed of fatty acids esterified to a platform molecule and contain other groups such as alcohols or sugars. Lipids spontaneously assemble into bilayers which are largely impermeable to charged and polar molecules and which form closed compartments. Key Concepts: Fatty acids Phospholipids Glycolipids Cholesterol Micelles Bilayers Vesicles Permeability of bilayers