VERSATILE GATEKEEPER 
"In the beginning," writes Gerald 
Weissmann of New York University, 
"there must have been a membrane! 
Whatever flash of lightning there was 
that organized purines, pyrimidines, 
and amino acids into macromole- 
cules capable of reproducing 
themselves, it would not have yielded 
cells but for the organizational trick 
afforded by the design of a mem- 
brane wrapping." Weissmann 
imagines these primitive membranes 
forming bubbles in which the first 
macromolecules were enclosed and 
protected from dissipation in the salty 
primordial seas. 
A cell's outer membrane is often 
thought of as a boundary that defines 
the living cell from its surroundings. 
And, indeed, surface membranes are 
crucial in keeping cells intact. More- 
over, the internal membranes that 
wrap around many organelles in 
eukaryotic cells separate the cyto- 
plasm into discrete regions, some- 
what like the walls that form rooms 
in a house. These inner membranes 
enable the cell to perform many 
biochemical activities simultaneously, 
thereby greatly increasing the cell's 
efficiency. 
Yet despite its barrier functions, the 
cell membrane — which is often less 
than 0.01 micrometer thick — is not 
impassive. Rather, it is exquisitely 
sensitive to its surroundings and 
selectively allows certain substances 
to enter and leave the cell while 
barring others. It takes in nutrients 
and excretes wastes. It sends and 
receives chemical and electrical 
messages, including signals for the 
cell to manufacture proteins or to 
divide. In multicellular organisms, it 
joins with other cells to form tissues. 
These myriad abilities are due to 
the membrane's composition. Al- 
though surface membranes differ in 
their precise composition depending 
on the cell's type, and although a 
membrane's configuration changes 
from moment to moment, all mem- 
branes are composed of two basic 
kinds of molecules — proteins and 
lipids (fats). 
In 1 972, S. Jonathan Singer and 
Garth Nicolson of the University of 
California, San Diego, proposed a 
model to describe the relationship of 
proteins and lipids in an idealized 
membrane. They compared the 
proteins to "icebergs floating in a 
sea of lipids," and suggested that 
some of the proteins are folded so 
that the "tips" poke above and 
below the plane of the membrane, 
while the middle of the protein is 
embedded in the membrane itself. 
Although such tripartite proteins 
were unknown at the time Singer 
and Nicolson proposed their model, 
they have since been shown to exist. 
Many other membrane proteins that 
are attached either to the inner or 
outer face of the surface membrane 
have also been studied in detail in 
the years since Singer and Nicolson 
proposed their so-called fluid-mosaic 
model. It is now known that the 
proteins do not float through the lipids 
unrestrained. Rather, they are teth- 
ered in a general region by slender 
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