When the first cells developed, how could they bring molecules from the environment into their living interior without the specialized structures found on the modern cell membrane? A research team from Massachusetts General Hospital (MGH) has found that the sort of very simple membrane that may have been present on primitive cells can easily allow small molecules - including the building blocks of RNA and DNA - to pass through. Their report will appear in the journal Nature and is receiving early online release.
"We have found that membranes made from fatty acids and related molecules - the most likely components of primitive cell membranes - have properties very different from those of the modern cell membrane, which uses specialized pumps, channels or pores to control what gets in and out," says Jack Szostak, PhD, of the MGH Department of Molecular Biology and Center for Computational and Integrative Biology, the report's senior author. "Our report shows that very primitive cells may have absorbed nutrients from their environment, rather than having to manufacture needed materials internally, which supports one of two competing theories about fundamental properties of these cells."
How nutrients could get into cells without the specialized mechanisms of the modern cell membrane has been a mystery. The environment in which primitive cells formed probably included many types of fatty acids, which could have been supplied through a couple of scenarios. Fatty-acid molecules could have been formed by the action of heat and minerals deep beneath the earth's surface and then brought to the surface through deep-sea vents, hot springs or geysers; or they could have come to the earth's surface on meteorites. No matter the original source, when fatty acids are concentrated in water, they will naturally assemble into membranes which then close into tiny spherical structures called vesicles.
Szostak's team carefully analyzed vesicles comprised of different fatty acid molecules and identified particular features that made membranes more or less permeable to potential nutrient molecules. They found that, while large molecules such as strands of DNA or RNA could not pass through fatty acid membranes, the simple sugar molecules and individual nucleotides that make up larger nucleic acids easily crossed the membrane.
To further explore the function of a fatty acid cell membrane, the researchers used activated nucleotides they developed for this study that will copy a DNA template strand without needing the polymerase enzyme usually required for DNA replication. After placing template molecules inside fatty-acid vesicles and adding the activated nucleotides to the external environment, they found that additional DNA was formed within the vesicles, confirming that the nucleotide molecules were passing through the fatty-acid membranes.
"Today we have complex cells living in a chemically simple environment, but the primitive environment was chemically very complex, allowing for the synthesis of complex organic chemicals that cannot be formed in today's environment," Szostak explains. "We think that the first cells were very simple and assembled from molecules present in localized environments on the early earth."
For many years, Szostak's team has been working on the development of a 'protocell' that would replicate probable features of the earth's first cells. "The chemistry of nucleic acid replication is the remaining hard part," he says. "We're putting a lot of effort into nucleic acid chemistry, but there are also other interesting and important questions - like how cells made the transition from very leaky early membranes to today's very impermeable membranes - that we are starting to study."
The Alex Rich Distinguished Investigator in Molecular Biology at MGH, Szostak is a professor of Genetics at Harvard Medical School and a Howard Hughes Medical Institute investigator. The study was supported by grants from the NASA Exobiology Program, the National Science Foundation and the National Institutes of Health. Sheref Mansy, PhD, is the lead author of the Nature article, and additional co-authors are Jason Schrum, Mathangi Krishnamurthy, PhD, Sylvia Tobe and Douglas Treco, PhD, all of the MGH Department of Molecular Biology.
Massachusetts General Hospital (www.massgeneral.org), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.