Ch 7 Membranes: Their Structure, Function, and Chemistry

The basis of membrane structure is the lipid bilayer

E. Gorter and F. Grendel; 1925; read langmuirs papers and thought his approach might help answer a ? regarding the surface of the red blood cells they worked with. extracted lipids from a known # of erthyocytes(red blood cells) and used langmuirs method to spread the lipids as a monolayer on the water surface. found the area of the lipid film was about twice the estimated total SA of the erythrocyte. concluded RBC plas.mem. consists of 2 lipid layers. made 2 errors: 1. underestimated by ~1/3 both the SA and of the RBC and 2. the amount of lipid present in the plas.mem. fortunately these errors canceled each other out- their conclusion was correct even tho their data was not. reasoned that it would be thermodynamically favorable for the nonpolar CH chains of each layer to face inward, hydrophilic faces therefore face outward. this work represented the 1st work to understand membranes at the molecular level. lipid bilayer they envisioned became the basis for the underlying assumption for each successive refinement in our understanding of membrane structure.

desaturase

Enzyme that introduces double bonds into CH chains of fatty acids to increase membrane fluidity

Lateral diffusion

Exchanging places w neighboring molecules in the same monolayer. Happens readily

cell fusion experiments

Frye and Edidin; the mobility of membrane proteins can be shown experimentally by the mixing of membrane proteins that occurs when cells from 2 different species (mouse and human) are fused and the membrane proteins are labeled w specific fluorescent antibodies. observed w fluorescence microscopy. anti-mouse antibodies=fluorescein=green anti-human antibodies= rhodamine=red. Sendai virus used for fusion of cells.

Singlepass membrane proteins

Have just one transmembrane segment w a hydrophilic carboxyl terminus extending out of the membrane on one side and a hydrophilic amino terminus protruding on the other side. Ex. glycophorin

Multipass membrane proteins

Have several transmembrane segments, ranging from 2 to 3 to 20 or more. Ex. " band 3 protein"-each of its 2 polypeptides span the lipid bilayer at least 6x w both the C terminus and N terminus on the same side of the membrane. Ex. bacteriohodopsin- serves halobacteria as a proton pump

Integral monotopic proteins

Intergral membrane protein that is known to be embedded in, and therefore to protrude from, only one side of the bilayer

Rotation (of phospholipids)

Is about its long axis, happens readily

Transverse diffusion

"flip-flop" from one monolayer to the other, is relatively rare. Occurs more frequently in nat'l membranes than in artificial bilyaers bc some membranes (smooth ER) have proteins called phospholipid translocators or flippases.

electrophoresis

A group of related techniques that utilize an electrical field to separate charged molecules. How quickly a molecule moves depends on charge and size.

Integral membrane proteins

Amphipathic molecules possessing one or more hydrophobic regions that exhibit and affinity for the hydrophobic interior of the lipid bilayer. Are difficult to remove from the membrane bc hydrophobic regions embedded in membrane interior. Treatment w a detergent is necessary to solubilize and extract integral membrane proteins.

lactoperoxidase (LP)

An enzyme used in a method for labeling proteins exposed on one or both surfaces of a membrane vesicle. When LP and 125^I are present in the soln outside a membrane vesicle, LP catalyzes the labeling of membrane proteins exposed on the outer membrane surface. if membrane vesicles are first incubated in a hypotonic medium to make them premeable to LP and then transferred to an isotonic soln containing 125^I but no external LP, proteins exposed on the inner membrane surface become labeled

Lipid-anchored membrane proteins

Are neither specifically peripheral nor integral but have characteristics of both. Are located on one of the surfaces of the lipid bilayer but are covalently bound to lipid molecules embedded w/n the layer. Covalent linkage to either fatty acid or an isoprenyl group.

Western blotting

Procedure where the polypeptides in a standard SDS-PAGE gel or a 2D SDS-PAGE gel are transferred directly to a nylon or nitrocellulose membrane that is placed flat against the gel. An electric field is used to transfer the proteins from the gel to the membrane, where they remain in the same relative positions that they occupied in the gel. is very useful in determining which proteins are present in or on a particular cell. ex. used for identity of certain immune system cells or specific types of cancer cells.

hydropathy (or hydrophobicity) plot

constructed by using a computer program to identify clusters of hydrophobic amino acids. the a.a. sequence is of the protein is scanned though a series of "windows" of about 10 amino acids at a time, w each successive window 1 a.a. further along in sequence

one of the most useful ways to characterize a specific membrane is to describe the ___________,_________________,__________________ and other molecules associated with it

particular enzymes, transport proteins, receptors

main classes of membrane lipids:

phospholipids, glycolipids, sterols

hopanoids

plas.mem. of at least some prokaryotes contain sterol like molecules called___________ that appear to substitute for sterols in membrane structures. is rigid and strongly hydrophobic w a short hydrophilic chaon extending from one side

bacteriprhodopsin

plasma membrane protein found in archaea, where its presence allows cells to obtain energy directly from sunlight. a a molecule called retinal- the same light absorbing molecule used by the human eye to detect light.

glycosylation

the addition of a carb side chain to a protein. occurs in ER or Golgi. involves linkages or carb either to the N of an amino group or the O of a hydroxyl group

intergral membrane proteins

embedded w/n the lipid bilayer, held in place by affinity for hydrophobic segments of the protein for hydrophobic interior of bilayer

Recent findings further refine our understanding of membrane structure

emphasis that membranes are not homogenous, freely mixing structures. protein/lipid ordering often occurs in microdomains known as lipid rafts

membranes

essential feature of every cell, defines the boundaries of the cell and its various internal compartments.

widely used approach for quantifying the rates at which membrane proteins diffuse:

flurorescence photobleaching recovery

glycolipids

formed by adding carbohydrate groups to lipids. some are glycerol based but most are derivatives of sphingosine and are called glycosphingolipids. ABO blood groups involve glycosphingolipids. several serious human diseases are known to result from impaired metabolism of glycosphingolipids. best known is tay-sachs Most common exs: cerebroside and gangliosides, which are esp prominent in the membranes of brain and nerve cells.

tight junctions

from seals that block the passage of fluids between cells.

cadherins

have extracellular sequences of amino acids that bind calcium ions and stimulate adhesion btwn similar cells in a tissue

adhesive junctions

hold cells together

site specific mutagenesis

identifies functionally important amino acids. used to examine the effect of specific changes in the amino acid sequence of a protein. the DNA sequence encoding a specific segment of the protein can be altered by changing particular nucleotides. the mRNA transcribed from the mutant DNA is then injected into living cells. the cells use the mRNA to direct the synthesis of a mutant protein, the functional properties of which can be easily determined.

antibodies

immune system proteins that recognize and bind to sepcific molecular antigens such as cell surface proteins found in the plas.mem. fluorescent antibodies= antiobdies +dye

glycocalyx

in many animal cells, the carb groups of plas.mem. glycoproteins and glycolipids protrude from the cell surface and produce a sugar coat called a ___________.

membrane reconstitution

involves the formation of artificial membranes from specific purified components. proteins are extracted from membranes w detergents and separated into their individual protein components. the purified proteins are the mixed together w phopholipids under conditions known to promote the formation of liposomes. liposomes can the be tested for their ability to carry out specific functions that are known, or thought, to be mediated by membrane proteins.

lipid-anchored proteins

not part of original fluid mosiac model, are essentially hydrophilic proteins and reside on membrane surfaces but they are covalently attached to lipid molecules that are embedded w/n the layer

Lipids are important components of membranes

overton and langmuir; Overton:1890s;working w cells of plant root hairs, observed that lipid-soluble substances penetrate readily into cells, whereas water soluble substances do not. concluded that lipids are present on the cell surface as some sort of coat Langmuir: 1900s; studied behavior pf the purified phopholipids by dissolving them in benzene and layering smaples of the benzene-lipid solution onto a water surface. as the benzene evaporated, molecules left were a lipid film one molecule thick- "monolayer" langmuir reasoned that phopholipids orient themselves on water such that their hydrophobic tails protrude away from the water. monolayer became the basis for further thought about the membrane structure in the early yrs of the 20th century.

mechanisms for restricting protein motility

1. membrane proteins aggregate w/n the membrane, forming large complexes that move on slugglishly if at all 2.mem. proteins form structures that become barriers to the diffusion of other mem. proteins 3. most common= the binding or anchoring of mem. proteins to structures located adjacent to one side of the membrane or the other. ex. many proteins of plas.mem. are anchored either to elements of the cytoskeleton on the inner surface of the membrane or to the extracellular structures

Application of molecular biology techniques to the study of membrane proteins

1. DNA sequencing 2. predicted a.a. sequence can be subjected to hydropathy analysis to identify the likely transmembrane segments of the protein. 3. knowing a.a. sequence allows investigator to prepare synthetic peptides that correspond to specific segments of the protein 4. antibodies made against peptides can be radioactively labeled and used to determine which segments are exposed on one side of the membrane or the other 5. site specific mutagenesis 6.DNA probe- isolate other DNA sequnces similar to the probe

Membrane protein types

1. Integral 2. Peripheral 3. Lipid anchored

Steps for electrophoresis of membrane proteins

1. Membrane fragments are solubilized w SDS which coats the polypeptides and gives them a net negative charge 2. A small sample of the solubilized polypeptides is placed into a well at the top of a gel of polyacrylamide that is held between two glass plates 3. An electrical potential is applied across the gel w the + charged anode attached to the bottom of the gel 4. This causes the - charged polypeptide molecules to move toward the bottom end of the gel, each forming a discrete band 5. Each polypeptide moves down the gel that is inversely related to its size 6. The gel is stained w a dye that binds to the polypeptides and makes them visible 7. Bands identified using ladder

membrane proteins in animal tissues

1. adhesive junctions 2. tight junctions 3.gap junctions

biological membranes play 5 related yet distinct roles:

1. define boundaries of the cell and its organelles 2. serve as sites for the specific proteins, esp enzymes and receptors 3. provide for and regulate transport processes 4. contain protein receptors needed to detect external signals 5. provide mechanisms for cell-to-cell contact adhesion and communication

Membrane protein functions:

1. enzymes- accounts for the localization of specific functions to specific membranes 2. electron transport proteins- involved in oxidative properties in mitochondria, chloroplasts, and plasma mem.s of prokaryotic cells 3. transport proteins: facilitate movement of nutrients such as sugars and a.a.s across membranes 4. channel proteins- provide hydrophilic passageways through otherwise hydrophobic membranes 5. transport ATPases- use the energy of ATP to pump ions across membranes 6. receptors- involved in recognizing and mediating the effects of specific chemical signals that impinge on the surface of the cell 7. intercellular communication- exs. connexons at gap junctions in animals, and plasmodesmata in plants 8. uptake and secretion of various substances by endo/exo-cytosis 9. targeting/sorting/modifying of proteins w/n the ER and golgi 10. detection of light- human eye, plant, bacteria 11. structual components- spectrin, ankyrin, band 4.1 protein 12. autophagy - "self eating"

3 classes of membrane proteins are now recognized based on differences in how the proteins are linked to the bilayer.

1. intergral membrane proteins- embedded w/n the lipid bilayer, held in place by affinity for hydrophobic segments of the protein for hydrophobic interior of bilayer 2. peripheral proteins- mcuh more hydrophilic and are located on surface of membrane, where they are linked noncovalently to the polar head groups of phospholipids and/or to the hydrophilic parts of other membrane proteins 3. lipid-anchored proteins- not part of original fluid mosiac model, are essentially hydrophilic proteins and reside on membrane surfaces but they are covalently attached to lipid molecules that are embedded w/n the layer

Kinds of movement of a phospholipid

1.Transverse diffusion 2. Rotation 3.Lateral Diffusion

Overton

1890s;working w cells of plant root hairs, observed that lipid-soluble substances penetrate readily into cells, whereas water soluble substances do not. concluded that lipids are present on the cell surface as some sort of coat. even suggested cell coats prob contain mixtures of cholesterol and lecithin

Langmuir

1900s; studied behavior pf the purified phopholipids by dissolving them in benzene and layering smaples of the benzene-lipid solution onto a water surface. as the benzene evaporated, molecules left were a lipid film one molecule thick- "monolayer" langmuir reasoned that phopholipids orient themselves on water such that their hydrophobic tails protrude away from the water. monolayer became the basis for further thought about the membrane structure in the early yrs of the 20th century.

Most membrane proteins contain transmembrane segments

1970s; most integral membrane proteins have in their primary structure one or more hydrophobic sequences that span the lipid bilayer. these transmembrane segments anchor the protein to the membrane and hold it in proper alignment w/n the lipid bilayer. Unwin and Henderson used e- microscopy to determine the 3D structure of unfixed, crystallized bacteriorhodopsin and its orientation in the membrane. (1975) finding that bacterio. consists of a single peptide chain folded back and forth across the lipid bilayer for a total of 7x.

A membrane consists of a mosaic of proteins in a fluid lipid bilayer

1972; S. Johnathan Singer and Garth Nicoloson. Fluid mosiac model, now dominates our view of membrane organization. envisions a membrane as a mosiac of proteins discontinuously embedded in, or at least attached to, a fluid lipid bilayer. Singer-Nicoloson model retained the basic lipid bilayer structure, but viewed membrane proteins in an entirely different way- not as thin sheets but as globular entities that associate bassed on relative affinities for hydrophobic interior. fluid nature- rather than being rigidly locked in place, most of the lipid components of a membrane are in constant motion capable of lateral motility. Fluid mosiac model readily explains criticisms of Davson-Danielli model.

Phospholipid translocators

Aka flippases. Catalyze the flip-flop of membrane lipids from one monolayer to the other. Act only on specific kinds of lipids.

Peripheral membrane proteins

Bound to membrane surfaces through weak electrostatic forces and H bonding w the hydrophilic portions of integral proteins and perhaps the polar head groups of membrane lipids. Ex. spectrin, Ankyrin and band 4.1

Phase transition

Change of a lipid bilayer from a solid-gel like state to a fluid.

Transition temperature (Tm)

Characteristic of every lipid bilayer. Emp at which layer becomes fluid (melts) when warmed from a solid gel-like state. To function properly a membrane must be maintained in the fluid state., that is a temp above the trans. Temp value.

Membrane asymmetry

Chemical studies involving membranes derived from a variety of cell types has revealed that most lipids are unequally distributed between the 2 monolayers. Includes differences both in kinds of lipids present and the degree of unsaturation of the fatty acids in the phospholipid molecules.

Sterols: ___________ in animals and _____________ in plants also affect membrane fluidity

Cholesterol; phytosterols

Fatty acids

Components of all membrane lipids except the sterols. Essential to membrane structure bc their long CH tails form an effective hydrophobic barrier to the diffusion of polar solutes. Most btwn 12-20 C atoms in length w 16- and 18- esp common. Chains <12 or >20 are less able to form a stable bilayer. Keep in mind bonding and that double bonds in the chain results in kinks that affect membrane fluidity.

Membranes also contain proteins

Davson and Danielli; simple lipid bilayer could not explain all properties of membranes such as surface tension, solute permeability, and electrical resistance. 1935; suggested that proteins are present in membranes. proposed that biological membranes consist of a lipid bilayer coated on both sides w a thin sheet of protein. original Davson-Danielli model was in essence a protein-lipid-protein sandwich. this model was the 1st rep. of the membrane organization and dominated the thinking of cell biologists for the next several decades. original model later modified: 1954- hydrophilic proteins might penetrate into the mebrane in places to provide polar pores thru an otherwise hyrdrophobic bilayer. real significance of this model: recognized the importance of proteins in membrane structure

Fluorescence recovery after photobleaching

Lateral diffusion of membrane lipids demonstrated by this. The investigator tags, or labels, lipid molecules in the membrane of a living cell by covalently linking them to a fluorescent dye. a high intensity laser beam is then used to bleach the dye in a tiny spot. If the cell surface is examined immediately after w a fluorescence microscope, a dark, nonfluorescent spot is seen on the membrane. w/n secs the edges of the spot become fluorescent as bleached lipids diffuse out of the laser-treated area and fluorescent lipid molecules from adjoining regions of the membrane diffuse in.

A major challenge to protein chemists has been the difficulty of isolating and studying membrane proteins, many of which are hydrophobic

Lipid anchored and peripheral proteins easily removed by changes in pH and ionic strength. Integral membrane proteins more difficult to isolate- use of detergents such as SDS (sodium dodecyl sulfate) is needed for isolation.

Lipid rafts

Localized regions of membrane lipids that are involved in cell signaling. Dynamic structures that change In composition as individual lipids move in and out of them. Are thicker and less fluid than the rest of the membrane, distinguishing them as discrete lipid microdomains. Signals that are detected by the receptor proteins in the outer monolayer are transmitted to the interior of the cell by functional links btwn the lipid rafts in the 2 membrane monolayers.

GPI-anchored membrane proteins

Made in the ER as singlepass transmembrane proteins that subsequently have their transmembrane segments cleaved off enzymatically and replaced by GPI anchors.

Transmembrane proteins

Majority of integral membrane proteins; span the membrane and have hydrophilic regions protruding from the membrane on both sides. Proteins cross the membrane either once, single pass proteins, or several times, multipass proteins

Homeoviscous adaptation

Most polikiotherms can compensate for temp changes by altering the lipid bilayer composition of their membranes, thereby regulating membrane fluidity. Called _____________- bc the main effect on such regulation is to keep the viscosity of the membrane approximately the same despite changes in temperature. Is important for hibernating animals as well.

Transmembrane segments

Most transmembrane proteins are anchored to the lipid bilayer by one or more hydrophobic ______________, one for each time the protein crosses the bilayer. Are usually separated along the primary structure of the protein by hydrophilic sequences that protrude or loop out on the 2 sides of the membrane. In most cases, polypeptide chain appears to span the membrane in an alpha helical conformation consisting of about 20-30 a.a. residues most of which have hydrophobic R groups.

Differential scanning calorimetry

One means of determining the transition temperature a given membrane. Monitors the uptake of heat that occurs during the transition from one physical state to another- the gel-to-fluid transition, in case of membranes. Membrane of interest is placed in a sealed chamber, the calorimeter, and the uptake of heat is measured as the temp is slowly increased. Point of max heat absorption corresponds to Tm

polikiotherms

Organisms such as bacteria, fungi, protozoa, algae, plants, invertebrates, "cold blooded" animals that cannot regulate their own temperature

Orientation of Cholesterol molecules in a lipid bilayer

Orients itself so its single hydroxyl group close to the polar heads. OH group forms a H bond with the O of the ester bond btwn glycerol backbone and a fatty acid. Nonpolar steroid rings and CH tail side groups interact.

Thin-layer chromatography (TLC)

Separates different kinds of lipids based on their relative polaritites. Lipids are solubilized from a membrane preparation using a micture of nonpolar organic solvents and separated using a glass plate coated w silici acid, a polar compound. A sample is applied to 1 end of the plate by spotting the extract onto a small area called the origin. After the solvent has evaporated the edge of the plate is dipped into a solvent system that typically consists of chloroform, methanol. And water. As the solvent moves up past the origin and up the plate by capillary action, the lipids are separated based on their polarity-relative affinities for the polar silicic acid (stationary phase) plate and the less polar solvent(mobile phase).

caveolae

Small, flask shaped invaginators of the plas.mem. contain the cholesterol-binding protein caveolin and are regarded as a subset of lipid rafts

Freeze fracturing

Technique in which a lipid bilayer or a membrane is frozen quickly and then subjected to a sharp blow from a diamond knife. Bc the nonpolar interior of the bilayer is the path of least resistance thru the frozen specimen , the resulting fracture often follows the plane btwn the 2 layers of membrane lipid. As a result, the bilayer is split into its inner and outer monolayers, revealing the inner surface of each. Strong support for the fluid mosaic model came from studies in which artificial bilayers and nat'l membranes were prepared for e- microscopy by ________________________. Conformation that the particles seen in this way really are proteins came from work by Deamer and Branton.

the effects of sterols on membrane fluidity

The intercalation of rigid cholesterol molecules into the membrane of an animal cell makes the membranes less fluid at higher temps than it would otherwise br. Cholesterol also effectively prevents the CH chains of phospholipids from fitting snugly together as the temp is decreased, therefore reducing the tendency of membranes to gel upon cooling. Thus cholesterol has the moderating effect of decreasing membrane fluidity at the temps above Tm and increasing it at temps below the Tm. Decrease the permeability of a lipid bilayer to ions and small polar molecules

A membrane's fluidity depends primarily on _______________________________. Lipid type variables that control fluidity:

The kinds of lipids it contains. 1. Length of fatty acid side chain 2. Degree of unsaturation Long chains have higher transition temps than short chains, therefore membranes composed of mostly long chains are less fluid. Unsaturated fatty acids majority composing a membrane= more fluid (#of bonds increase and so does fluidity) most unsaturated fatty acids contain cis double bonds, in contrast many commercially processed fats contain trans double bonds, which resemble saturated fats more closely.

Fatty-acid anchored membrane proteins

The protein is synthesized in the cytosol and then covalently attached to a sat. fatty acid embedded w/n the membrane bilayer. Type of lipid anchored protein

Isoprenylated membrane proteins

Type of lipid-anchored protein. Synthesized as soluble cytosol proteins before being modified by addition of multiple 5-carbon isoprenyl groups, usually in the form of a 15-carbon farnesyl group or 20-carbon geranylgeranyl group. After attachment the f. or g. group is inserted into the lipid bilayer of the membrane.

gap jucntions

allow for some of the exchange of cellular components

hydropathic analysis

alternative to x-ray crystallography to determine 3d structure of membrane proteins that cannot be isolated in crystalline form.

ganglioside

always has an oligosaccharide head group that contains one or more negatively charged sialic acid residues and gives the molecule a net negative charge. function as antigens recognized by antibodies in immune rxns.

shortcomings of the Davson-Danielli model

as more membranes were studied, it became increasingly difficult to reconcile such enormous variations in protein content with the unit membrane model proposed by Robertson, bc the width and appearance of the "rails" simply did not vary correspondingly

Membrane proteins are oriented ______________ across the lipid bilayer

asymmetrically

hydropathy index

based on the known hydrophobicity values for the various a.a.s; calculated for each succesive window by averging the hydrophobivity valus of the a.a.s in the window. hydrophobic a.a.s have + hydropathy values, hydrophilic residues have - values. Ex. connexin is thought to have 4 transmembrane segements as a result of its hydropathy plot.

cerebrosides

called neutral glycolipids bc each molecule has a single uncharged sugar as its head group

galactose oxidase (GO)

can be used to label carb. side chains that are attached to membrane proteins or lipids

autophagy

cells digest their own organelles or structures that become damaged or are no longer needed. in this wat, molecular components of these structures can be recycled and reused in newly synthesized structures

sterols

main sterol in animal cells is cholesterol, which is necessary for maintaining and stabilizing membranes in our bodies. plants have small amounts of cholesterol and large amounts of phytosterols. fungal membranes contain ergosterol(targer of anitfungal meds). Sterols not found in membranes of most bacterial cells, but found in mycoplasma. sterols absent in mitochondira and chloroplasts

peripheral proteins

mcuh more hydrophilic and are located on surface of membrane, where they are linked noncovalently to the polar head groups of phospholipids and/or to the hydrophilic parts of other membrane proteins

glucose phosphatase

membrane bounded enzyme found in the ER and its presence in, say, a preparation of mitochondria would demonstrate contamination w ER membranes

glycoproteins

membrane proteins w carb. chains linked covalently to a.a. side chains. carb chains can either be straight or branched and range in length from 2-60 sugar units. carb chains always protrude on outer surface

phospholipids

most abundant lipids found in membranes. membranes contain many different types of phospholids: 1.glycerol based phosphoglycerides 2.and sphingosine based sphingolipids. sphingomyosine is one of the main components of animal plas.mem. but absent from plas.mem. from must plant and bacterial

intracellular membranes

serve to compartmentalize functions w/n eukaryotic cells.

receptors

specific proteins on the outer surface of cells, signal molecules bind to this. ex. liver cells have insulin receptors and can therefore respond to that hormone

plasma membrane

the permeability barrier for the cell as a whole. surrounds the cell and regulates the passage of materials both into and out of the cells

signal transduction

the term used to describe the specific mechanisms used to transmit such signals from t he outer surface of the cell to the cell interior

fluid mosiac model

thought to be descriptive of all biological membranes. envisions a membrane as 2 quite fluid layers of lipids w proteins localized w/n and on the lipid layers and oriented in a specific manner w respect to the 2 membrane surfaces.

x-ray crystallography

used to determine 3d structure of membrane proteins; determines structure of proteins that can be isolated in crystalline form. Michel, Deisenhofer, Huber shared Nobel Prize in 1988 for first success of this technique.

affinity labeling

utilizes radioactive molecules that bind to specific membrane proteins bc of known functions of proteins

All membranes share a common underlying stucture

w advent of electron microscopy in the 1950s, cell biologists could finally verify the presence of a plas.mem. could also observe membranes around organelles. when membranes stained with osmium, found to have extensive regions of "railroad track structure" J. David Robertson suggests that all cellular membranes share a common underlying structure which he called a unit membrane.