Membrane models

Article discusses the cell membrane models proposed from the years 1880 to 2000, which all led to the discovery of the current fluid mosaic model of membranes.

Before the emergence of electron microscopy in the 1950s, scientists and researchers did not know what the structure of a cell membrane looked like or what components made up a cell membrane. To assist in comprehending the concept of cells, researchers and biologists used indirect evidence to create an understanding of membranes before the membranes could actually be visualized. It is with these specific models of Overton, Langmuir, Gorter and Grendel, and Davson and Danielli, we can clarify that membranes have lipids, proteins, and a bilayer. After the creation of the electron microscopes, the findings of J. David Robertson, the proposal of Singer and Nicolson, and the additions of Unwin and Henderson contributed to the making of the modern membrane model. However, a further understanding of the past membrane models elucidates our perception of the present membrane visual. With intense experimental research, the membrane models of the precedent century made way for the fluid mosaic model (with refined additions), used today.

Gorter and Grendel's membrane theory (1925)

Diagram of the arrangement of amphipathic lipid molecules to form a lipid bilayer. The yellow polar head groups separate the grey hydrophobic tails from the aqueous cytosolic and extracellular environments.

Evert Gorter and F. Grendel (Dutch physiologists) approached the discovery of our present model of the plasma membrane structure as a lipid bilayer. They simply hypothesized that if the plasma membrane is a bilayer, then the surface area of the monolayer of lipids measured would be double the surface area of the plasma membrane. To examine their hypothesis, the experiment performed was the extraction of lipids from a known amount of red blood cells (erythrocytes) of different mammalian sources, such as humans, goats, sheep etc. and then by spreading the lipids as a monolayer on a Langmuir-Blodgett trough. They measured the surface area of the plasma membrane of red blood cells, and by using Langmuir's method, they measured the area of the monolayer of lipids. By comparing these two, they calculated an estimated ratio of 2:1(_{Monolayer of lipids: Plasma membrane}). This supported their hypothesis, which led to the conclusion that cell membranes are composed of two opposing molecular layers. Gorter and Grendel proposed the structure of this bilayer, the polar hydrophilic heads facing outwards towards the aqueous environment and the hydrophobic tails facing inwards away from the aqueous surroundings on both sides of the membrane. Although they had correct conclusions, parts of the data collected from the experiment were incorrect including calculation of the monolayer of lipids area and pressure, and incomplete lipid extraction. They failed to describe membrane function, and had false assumptions such as the plasma membrane consisting of mostly lipids. On the other hand, this envision of the lipid bilayer structure became the basic underlying assumption for each successive refinement in our modern understanding of membrane function.

The Davson and Danielli model with backup from Robertson (1940–1960)

File:MembranaAspectoTrilaminar.jpg

Trilaminar appearance of cell membrane

Following the proposal of Gorter and Grendel, inevitable questions arose about the clarity of having just a simple lipid bilayer as a membrane. Their model wasn't suitable to answer the relations of surface tension, permeability, and the electric resistance of membranes. Therefore, physiologist Hugh Davson and biologist James Danielli suggested that membranes indeed do have proteins. The existence of these "membrane proteins" would explain that which couldn't be answered by the Gorter and Grendel model. In 1935, Davson and Danielli proposed that biological membranes are made up of lipid bilayers which are coated on both sides with thin sheets of protein. They simplified their model into the "pauci-molecular" theory. The theory declared that all biological membranes have a "lipoid" center surrounded by monolayers of lipid and are covered by protein monolayers. In short, their model was illustrated as a "sandwich" consisting of protein-lipid-protein. The Davson and Danielli model made way for the rudimentary understanding of cell membranes, and stressed the importance of proteins in biological membranes.

By the 1950s, cell biologists verified the existence of plasma membranes due to the creation of the electron microscope (which accounted for higher resolutions). J. David Robertson used this tool (electron microscopy) to propose the unit membrane model. Basically, he suggested that all cellular membranes share a similar underlying structure, the unit membrane. Using heavy metal staining, Robertson's proposal also seemed to agree instantaneously with the Davson and Danielli model. According to the trilaminar pattern of the cellular membrane viewed by J. David, he suggested that the membranes consist of a lipid bilayer covered on both surfaces with thin sheets of proteins. This suggestion gave great support to the proposal of Hugh Davson and James Danielli. However, even with Robertson's substantiation great complications came with the Davson and Danielli model. One main complication being, that the membrane proteins studied were mainly globular and wouldn't fit into the model's claim of thin sheets of proteins. Along with these arising complications of the Davson and Danelli model, interest in finding new ways of membrane organization stimulated and made way for the fluid Mosaic model which was proposed in 1972.

Singer and Nicolson's fluid mosaic model (1972)

In 1972, S. Jonathan Singer and Garth Nicolson developed new ideas for membrane structure. Their proposal was the fluid mosaic model, which is the dominant model so far. It has two key features, a mosaic of proteins embedded in the membrane, and the membrane being a fluid bilayer of lipids. The lipid bilayer suggestion agrees with previous models but views proteins as globular entities embedded in the layer instead of thin sheets on the surface.

Membrane proteins are sorted into three classes based on how they are linked to the lipid bilayer:

1. Integral proteins: immersed in the bilayer and held in place by the affinity of hydrophobic parts of the protein for the hydrophobic tails of phospholipids on interior of the layer.
2. Peripheral proteins: more hydrophilic, thus are noncovalently linked to the polar heads of phospholipids and other hydrophilic parts of other membrane proteins on the surface of the membrane.
3. Lipid anchored proteins: essentially hydrophilic, so, are also located on the surface of the membrane, and are covalently attached to lipid molecules embedded in the layer.

As for the fluid nature of the membrane, the lipid components are capable of moving parallel to the membrane surface and are in constant motion. Many proteins are also capable of that motion within the membrane. However, some are restricted in their mobility due to them being anchored to structural elements such as the cytoskeleton on either side of the membrane.

In general, this model explains most of the criticisms of the Davson–Danielli model. It eliminated the need to accommodate membrane proteins in thin surface layers, proposed that the variability in the protein/lipid ratios of different membranes simply means that different membranes vary in the amount of protein they contain, and, it shows how the exposure of lipid head groups at the membrane surface is compatible with their sensitivity to phospholipase digestion. Also, the fluidity of the lipid bilayers and the intermingling of their components within the membrane make it easy to visualize the mobility of both lipids and proteins.

Singer and Nicolson's fluid mosaic model

Henderson and Unwin's membrane theory

Transient receptor potential cation channel subfamily V member 1 (TRPV1). Ion channels are integral membrane proteins of great importance for living organisms.

Henderson and Unwin have studied the purple membrane by electron microscopy, using a method for determining the projected structures of unstained crystalline specimens. By applying the method to tilted specimens, and using the principles put forward by De Rosier and Kulg for the combination of such two-dimensional views, they have obtained a three dimensional map of the membrane at 7 A resolution. The map reveals the location of the protein and lipid components, the arrangement of the polypeptide chains within each protein molecule, and the relationship of the protein molecules in the lattice.

High-resolution micrographs of crystalline arrays of membrane proteins, taken at a low dose of electrons to minimize radiation damage, have been exploited to determine the three-dimensional structure by Fourier transform. Recent studies on negatively stained rat hepatocyte gap junctions subjected to three-dimensional Fourier reconstruction (of low-dose electron micrographs) indicate that the six protein subunits are arranged in a cylinder slightly tilted tangentially, enclosing a channel 2 nm wide at the extracellular region. The dimensions of the channel within the membrane were narrower but could not be resolved (Unwin and Zampighi, 1980). A small radical movement of the subunits at the cytoplasmic ends could reduce the subunit inclination tangential to six-fold axis and close the channel.

Further details of the molecular organization should emerge as preparative methods become available so that high-resolution three dimensional images comparable to the purple membranes. By using ingenious procedure for the analysis of periodic arrays of bio macromolecules in which data from low-dose electron images and diffraction patterns were combined (Henderson and Unwin (1975)), reconstructed a three-dimensional image of purple membranes at 0.7 nm resolution. Glucose embedding was employed to alleviate the dehydration damage and low doses (<0.5 e\A) to reduce the irradiation damage. The electron micrographs of unstained membranes were recorded such that the only source of contrast was a weak phase contrast induced by defocusing.

In their experiment, Unwin and Henderson found that protein extends to both sides of the lipid bilayer and is composed of seven α-helices packed about 1-1.2 nm apart, 3.5-4.0 nm in length, running perpendicular to the plan of membrane. The molecules are organized around a threefold axis with a 2 nm-wide space at the center that is filled with lipids. This elegant work represents the most significant step forward thus far, as it has for the first time provided us with the structure of an integral membrane protein in situ. The availability of the amino acid sequence, together with the information about the electron scattering density from the work of Henderson and Unwin (1975), has stimulated the model-building efforts (Engleman et al., 1980) to fit the bacteriorhodopsin sequence information into a series of α- helical segment. Some of the features of the model proposed by Engleman et al.

See also

• Cell biology
• History of cell membrane theory
• Fluid mosaic model
• Cell theory
• Cell membrane
• Lipid
• Membrane protein