October 24, 2003
Clays May Have Aided Formation of Primordial Cells
Howard Hughes Medical Institute (HHMI) researchers have discovered
that clays may have been the catalysts that spurred the spontaneous
assembly of fatty acids into the small sacs that ultimately evolved
into the first living cells.
HHMI investigator Jack W.
Szostak and colleagues Martin M. Hanczyc and Shelly M. Fujikawa at
Massachusetts General Hospital also demonstrated that these vesicles
could be induced to grow and to split into separate vesicles under
laboratory conditions. They reported their studies in the October 24,
2003, issue of the journal Science.
“We are not claiming that this is how life started. We are saying that we have demonstrated growth and division without any biochemical machinery.”
Jack W. Szostak
Szostak and his colleagues were prompted to perform their
experiments by the earlier work of other researchers who had found that
clays could catalyze the chemical reactions needed to construct RNA
from building blocks called nucleotides. They reasoned that if clays
could foster the formation of vesicles, it would not be inconceivable
that clay particles that had RNA on their surface could end up inside
such vesicles. If that were true, the result would offer conditions
amenable to the eventual evolution of living cells that could
self-reproduce.
“Other researchers had observed that if fatty acid micelles,
which are stable at basic conditions, are exposed to more acidic
conditions, they spontaneously assemble into vesicles,” said
Szostak. “This reaction has a long lag period, and some sort of
nucleation surface is required to trigger the process. We reasoned that
if the right kind of mineral surface was present, this lag phase would
be eliminated.”
In their experiments, Szostak and his colleagues found that adding
small quantities of the clay, montmorillonite, to fatty acid micelles
greatly accelerated the formation of vesicles. They also discovered
that many other substances with negatively-charged surfaces also
catalyzed formation of vesicles.
When the researchers loaded montmorillonite particles with a
fluorescently labeled RNA and added those particles to micelles, they
detected the RNA-loaded particles inside the resulting vesicles. And,
going a step further, Szostak and his colleagues showed that when they
encapsulated labeled RNA alone inside vesicles, it did not leak
out.
“Thus, we have demonstrated that not only can clay and other
mineral surfaces accelerate vesicle assembly, but assuming that the
clay ends up inside at least some of the time, this provides a pathway
by which RNA could get into vesicles,” said Szostak.
However, he said, even primitive, non-living, cell-like structures
need a mechanism to grow and divide. Thus, the scientists explored the
behavior of vesicles to which micelles had been added — finding that
acidic conditions induced the micelles to become unstable and somehow
incorporate themselves into a growing vesicle.
“After we showed that efficient growth was possible, the next
problem was how to complete the cycle by persuading these vesicles to
divide,” said Szostak. The scientists discovered that if they
extruded larger dye-containing vesicles through smaller pores, the
result was a proliferation of smaller vesicles, which still contained
dye.
“Exactly how this proliferation happens is not clear, and
there are different models for the processes,” said Szostak.
“The important thing is that it all works. You end up with small
vesicles in which the contents stay mostly inside. This is important if
the process is to be vaguely analogous to biological cell
division,” he said.
“Now that we have a proof-of-principle that growth and
division is possible in a purely physical-chemical system, we are
working on a way to get this cycle to function in a way that is more
natural,” said Szostak. “Clearly, there are a lot of
complicated and interesting processes going on here, and how this
pathway leads to biological systems is not at all straightforward.
“We are not claiming that this is how life started,”
emphasized Szostak. “We are saying that we have demonstrated
growth and division without any biochemical machinery. Ultimately, if
we can demonstrate more natural ways this might have happened, it may
begin to give us clues about how life could have actually gotten
started on the primitive Earth.”
In particular, said Szostak, further research should aim to
demonstrate that the formation of RNA or a related polymer molecule
could occur concurrently with vesicle replication. “Ultimately,
we'd like to put them together and have replicating RNA inside a
replicating vesicle,” said Szostak. “If we could
demonstrate both processes under arbitrary laboratory conditions, we
could begin to work toward making them work under more and more natural
conditions.”
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