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Singer and Nicolson (1972) described the plasma membrane as a mosaic of proteins and phospholipids in a fluid phospholipid matrix . To do this, however, they needed to a) provide evidence that membrane proteins were actually embedded within the membrane and b) determine whether the membrane's matrix was protein or lipid in structure as both types of biological molecules constitute major components of the membrane.
Experimental results published in 1971 suggested that proteins were randomly, not regularly, distributed as predicted by the lipid model (Nicolson, Masouredis, and Singer, 1971; Nicolson, Hyman, and Singer, 1971). However, these results did not bear on the second prediction of the lipid matrix model: , that the distribution of integral proteins would be dynamic , that is, would change through time as the proteins diffused through the fluid lipid matrix (Singer and Nicolson, 1972).
To support this second prediction, Singer and Nicolson (1972) cited an elegant experiment published in 1970 by L.D. Frye and M. Edidin. The goal of Frye and Edidin's study had been to demonstrate that the plasma membrane was fluid in nature, an attribute they felt had been ignored by certain models of membrane structure. As they wrote in the introduction to their paper,
The surface of membranes of animal cells rapidly change shape as the cells move, form
pseduopods , or ingest materials from their environment. These rapid changes in shape suggest
that the plasma membrane itself is fluid, rather than rigid in character, and thatat least some of its component macromolecules are free to move relative to one another
within the fluid. We have attempted to demonstrate such freedom of movement usingspecific antigen markers of 2 unlike unlike cell surfaces. (Frye and Edidin, 1970, p.320)
To demonstrate the membrane's fluidity, Frye and Edidin created hybrid cells or ‘heterokaryons’ by fusing a human cell with a mouse cell to form a single cell with a continuous plasma membrane containing both human and mouse specific integral proteins. After fusion, the distribution of proteins on the cell surface was tracked for several hours using chemical stains that differentiated human from mouse proteins. The spatial distribution of proteins in these ‘double-stained cells’ were compared to control preparations of human-human fused and mouse-mouse fused cells which stained exclusively the color specific to human or mouse proteins respectively (Frye and Edidin, 1970). Frye and Edidin’s results appear in Figure 1 below.
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