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April 3, 2006

Chemist explores the membranous origins of the first living cell

By Chandra Shekhar

Blowing bubbles is child's play, showing how easily soap molecules can assemble into a sheet and curl around to form a bubble.

Photo: David DeamerDavid Deamer pours a "prebiotic soup" of chemicals into a volcanic pool in Kamchatka, Russia, to test a hypothesis about the origins of life.
Photo by Tony Hoffman

To David Deamer, professor of chemistry and biochemistry and acting chair of biomolecular engineering at UCSC, the formation of a soap bubble is no mere curiosity--it illustrates an essential property of the kinds of molecules that compose the membranes of all living cells.

While other researchers debate whether DNA or proteins came first, Deamer traces the origin of life to microscopic bubblelike membranes.

"Membranous boundary structures define all life today," he said. "A source of membrane-bounded microenvironments on the early Earth was essential for the rise of cellular life."

Deamer has been investigating the origins of life for more than 20 years, with continuous funding from NASA's Exobiology and Astrobiology Programs. In the 1980s, he demonstrated that meteorites contain molecules capable of forming stable membranes. More recently, he has ventured from the laboratory into the field to test ideas about the kind of environment where life could have begun.

Charles Darwin, in a letter to his friend J. D. Hooker in 1871, speculated about life beginning in a "warm little pond." Many scientists, however, now believe that life may have begun in extreme environments such as undersea hydrothermal vents and volcanoes, with their abundance of chemicals and energy. While many scientists have attempted to test this hypothesis in the laboratory, Deamer was the first to do so in the field.

In June 2005, he led a team of scientists, including Russian geologist Vladimir Kompanichenko, to the Kamchatka region in eastern Russia, an area abounding in pools of water heated and sterilized by constant volcanic activity. Deamer carried with him a version of the "primordial soup"--a mixture of compounds like those a meteorite could have delivered to the early Earth, including a fatty acid, amino acids, phosphate, glycerol, and the building blocks of nucleic acids. Finding a promising-looking boiling pool on the flanks of an active volcano, he poured the mixture in and then took samples from the pool at various intervals for analysis back in the lab at UCSC.

The results were strikingly negative: life did not emerge, no membranes assembled themselves, and no amino acids combined into proteins. Instead, the added chemicals quickly vanished, mostly absorbed by clay particles in the pool. Instead of supporting life, the bubbling pool had snuffed it out before it began. Later, Deamer repeated the same experiment at Lassen Volcanic National Park in northern California, with the same negative result.

What went wrong? The explanation is simple, said Deamer, who presented his findings in February at a meeting of the Royal Society of London. Conditions in geothermal springs and similar extreme environments just do not favor membrane formation, which is inhibited or disrupted by acidity, dissolved salts, high temperatures, and calcium, iron, and magnesium ions. Furthermore, mineral surfaces in these clay-lined pools tend to remove phosphates and organic chemicals from the solution.

"We have to face up to the biophysical facts of life," Deamer said. "Hot, acidic hydrothermal systems are not conducive to self-assembly processes. But these results serve to guide us to other possible sites that might be better choices."

A more benign environment for membrane formation, according to Deamer, would be a pool of relatively fresh water at moderate temperature ranges and with low acidity--something not very different from Darwin's "warm little pond." Next year, Deamer plans to find such a site near the Kilauea volcano on the Big Island of Hawaii and repeat the experiment there.

Meanwhile, Deamer and postdoctoral researchers Sudha Rajamani and Sara Singaram continue to explore the formation of membrane structures and replicating molecules in the laboratory. Even the most rudimentary cell membrane is far more than a bag of chemicals, Deamer said. It provides a stable compartment for the chemicals inside to interact. It supplies energy needed for nucleic acids to replicate and proteins to be synthesized. It allows nutrients from outside to enter the cell and expels ions from the cell when necessary. Finally, it must be able to grow and divide.

"These are challenging requirements for life to emerge, but we can be optimistic," Deamer said. "The first cellular forms of life spontaneously overcame all these hurdles."

The cell membrane's stability and versatility come from a special quality of the molecules it is made from: one end of each molecule is soluble in water, while the other end is repelled by it. Dissolved in water at a sufficient concentration, such "amphiphilic" molecules (as chemists call them) can assemble into fluid-filled bubbles called "vesicles."

Deamer speculates that the first membranes were made of simpler chemicals than the complex molecules that form modern cell membranes. And he has shown that meteorites could have delivered simple amphiphilic molecules to the Earth.

"Amphiphilic molecules present in carbonaceous meteorites can form stable membranes," Deamer said. "They are also produced in laboratory simulations of volcanic conditions, so it seems very likely that such molecules were present on the early Earth, along with many other kinds of organic compounds. This is of immense significance to the origin of cellular life."

Nobody was present to witness the birth of life, but Deamer's findings suggest a scenario something like the following: Four billion or so years ago, comets, meteorites, and interplanetary dust were delivering organic compounds to the Earth at a rate thousands of times greater than what occurs today. Together with compounds produced by volcanic reactions, the organic material was deposited in the ocean and on land masses resembling present-day Iceland or Hawaii. The organic material, along with phosphate, accumulated in small pools fed by intermittent rain.

Nothing much happened for a while. The pools behaved like a million others, growing in the rain and drying out in the sun. But during each dry spell, the organic compounds became a thin film covering the surfaces of the lava rock, and this allowed reactions to occur that could not take place in the dilute solution. Amphiphilic molecules that had been dispersed in the water began to organize first into sheets, and then into microscopic vesicles that trapped some of the other chemicals inside them.

Most of the vesicles did not have properties that were conducive to further evolution, but a few had trapped just the right mix of chemicals--amino acids, nucleotides, phosphates, and sugars. Protected from the environment, the chemicals in the vesicles began to react with one another to produce long molecular strings resembling the nucleic acids and proteins found in modern cells. These, in turn, began to interact in ways that researchers don't yet understand, but the end result was a system of encapsulated molecules that could grow and make more of themselves.

At some point, the vesicles found a way not only to grow, but also to reproduce by dividing into two or more nearly identical yet smaller structures that we would now call living cells.

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