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Thus, they reasoned that membrane proteins in a cell will assume globular (folded) conformations, due to hydrophobic and hydrophilic amino acid residues interacting with each other and the solvent environment, not the unfolded structures suggested by the DDR model. Similarly, membrane proteins will not be positioned to prevent contact between the polar head groups of membrane lipids and the aqueous cytoplasm.

So, if membrane proteins are globular and not layered on top of the membrane, where are they? How are they associated with the membrane?

The mosaic element of Singer and Nicolson's (1972) fluid mosaic model answered these questions. According to this model, membrane proteins come in two forms: peripheral proteins , which are dissolved in the cytoplasm and relatively loosely associated with the surface of the membrane, and integral proteins , which are integrated into the lipid matrix itself, to create a protein-phospholipid mosaic (Figure 2; Singer and Nicolson, 1972).

Original figure from Singer and Nicolson (1972) depicting membrane cross section with integral proteins in the phospholipid bilayer mosaic. Phospholipids are depicted as spheres with tails, proteins as embedded shaded, globular objects. Peripheral proteins, which would be situated at, not in, the membrane surface, are not shown. Recall that both surfaces of this membrane intercept an aqueous environment either the cytoplasm and/or the interstitial fluid. Transmembrane protein spanning entire membrane on left.

Singer and Nicolson (1972) supported these categories of proteins and their physical arrangement with both physical and biochemical evidence. For example, researchers had successfully separated the bilayers of frozen plasma membranes from a variety of sources including vacuoles, nuclei, chloroplasts, mitochondria and bacteria to reveal proteins embedded within (Singer and Nicolson, 1972). Similarly, evidence had also emerged to support the existence of transmembrane proteins, proteins that traversed the entire plasma membrane and extended into the aqueous environment on either side of the membrane (Figure 2).

Clear data supporting the predicted biochemical structure of integral proteins was harder to gain, however, and would only follow many years after the publication of the model. What was the biochemical structure of these proteins predicted to be?

Consider the energetic principles and molecular interactions on which Singer and Nicolson's model is based. Use your understanding of how these principles influence the structure and organization of individual polypeptides and the structural components of cells to answer the following questions.

1. Examine Figure 2. Predict biochemical properties (for example the hydrophobic or hydrophilic regions) of an integral protein versus those of a peripheral protein. Please be sure to explain your reasoning.

2. How do your predictions of the biochemical nature of integral proteins compare to Singer and Nicolson's predictions (Figure 3) adapted from a figure published by Lenard and Singer in 1966? If your predictions differ, please be sure to explain how and why they do.

Original figure from Singer and Nicolson (1972) depicting membrane cross section with integral proteins in the phospholipid bilayer. The ionic and polar portions of the proteins, as indicated by the +/- signs, contact the aqueous solutions (cytoplasm and/or interstitial fluid) surrounding the lipid bilayer. The membrane spanning or inserted region of the protein is non-polar/hydrophobic and therefore lacks charge as indicated by the absence of +/- symbols.

    Works cited

  • Eichman, P. 2007. (External Link) SHiPS Resource Center for Sociology, History and Philosophy in Science Teaching
  • Lenard, J. and S.J. Singer. 1966. Protein conformation in cell membrane preparations as studied by optical rotatory dispersion and circular dichroism. Proceedings of the National Academy of Sciences . 56:1828-1835.
  • Singer, S.J. and G. L. Nicolson. 1972. The fluid mosaic model of the structure of cell membranes. Science. 175: 720-731.
  • Singer, S.J. 1992. The structure and function of membranes - a personal memoir. Journal of Membrane Biology. 129:3-12.

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Source:  OpenStax, Discovering the structure of the plasma membrane. OpenStax CNX. Oct 15, 2007 Download for free at http://cnx.org/content/col10470/1.1
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