Fatty acid vesicles (cellular membranes) formed naturally in the early solar system. The proof is in meteorites. In the last three decades, Dr. Szostak and others have conducted laboratory experiments on natural protocell formation from fatty acid vesicles. They first tried to show that fatty acid vesicles could evolve on their own and later included internal RNA or other chemicals within the fatty acid vesicle. The advantage of an isolated cell that contains RNA and other molecules is that the internal contents of the cell are protected from the environment.
In one of the many attempts to envision how life might have started, Dr. Bruce Damer envisions early protocells forming from lipids (fatty acid vesicles) in ponds supplied by geysers. Geysers that form ponds might leave a ring around the pond, which would form the chemicals of life. It would form lipids on the walls of the pond. The lipids would form vesicles (spherical protocells) when they dissolved in the water. They might include RNA on the inside of the vesicles that might perform useful functions. The protocells with useful tools might survive longer than other protocells, thus leading to natural selection.
Dr. Szostak’s laboratory has conducted many experiments on growth and division of fatty acid vesicles and on their ability to conserve internal contents, such as RNA, when they divide. At some point in the process of evolution, RNA was incorporated into fatty acid vesicles. Experiments showed that vesicles grow and divide repeatedly while conserving internal contents.[1] [2] In 1994, Walde et al. demonstrated natural growth of fatty acid vesicles (autocatalytic growth) by absorption of fatty acids on vesicle surfaces.[3] Szostak’s group inserted RNA into vesicles and showed that larger vesicles filled with RNA removed material from smaller vesicles and grew while the smaller vesicles shrank, which they interpretated as evidence that evolution could take place.[4] The lab then demonstrated energy storage; as the vesicles grew, they could develop a higher concentration of hydrogen ions (protons) inside the vesicle.[5] Stored hydrogen is a form of energy storage in cells. Protocell vesicles would have needed to divide and grow in order for evolution to take place. Researchers have shown that the vesicles elongate in water and then divide into smaller protocells, conserving all internal contents during protocell division. The capability to conserve internal contents is important because if protocells were to evolve toward a biochemical system, then catalysts that would cause the formation of RNA and other moleucles would have needed to remain within the lipid membranes and not leak into the surrounding environment. External forces such as waves or by chemical changes in the protocell cause elongation.[6] Once the vesicles divide, more fatty acids added to the solution naturally become part of the vesicles and make them larger, and the process continues.
One potential problem with RNA and vesicles is that the copying chemistry of RNA requires a high fraction of magnesium, but magnesium normally disrupts fatty acid membranes and would destroy the protocell; however, there is a solution to this potential roadblock. Szostak’s team found that citric acid protected membranes from magnesium but also allowed for RNA copying within a fatty acid vesicle. Although citric acid was not part of prebiotic chemistry, this demonstrates that a molecule like citric acid might have protected protocells from disruption.
In modern cells, cellular processes must take place over a range of external and internal conditions. For example, the formation of messenger RNA takes place over a range of nitrogen concentrations within or external to the cell. The constancy of cellular processes in the midst of changing external or internal conditions is homeostasis. Modern cells regulate their internal conditions and processes with complex cellular proteins that regulate processes over a range of conditions. Organisms also demonstrate homeostasis at a macroscale. For example, humans maintain a body temperature of approximately 98.6 F in spite of changing external temperatures and varying levels of physical activity. The advantage of protocells over RNA chemistry in the open environment is that they might have maintained internal homeostasis over a range of external environmental conditions.
Engelhart et al (2016) tried to cause homeostasis in a protocell by regulating an RNA enzyme. The hammerhead ribozyme forms from two oligonucleotides, HH-A and HH-B. It also catalyzes the self-cleavage of HH-A.[7] Englehart added inhibitors with 5-7 nucleotides with complementary sequences with HH-B. By adding the right inhibitors, they inhibited the function of the hammerhead ribozyme at high concentrations of RNA, which would have acted as a homeostasis mechanism in a protocell. They then added the mix of ribozymes and inhibitors to a fatty acid vesicle (protocell) and found that they could maintain homeostasis as the protocell grew.
[1] I.A. Chen, K. Salehi-Ashtiani, and Jack Szotak. RNA Catalysis in Model Protocell Vesicles. J. Am. Chem. Soc. 127 (2005): 13213-13219.
[2] M.M. Hanczyc, S.M. Fujikawa, and J.W. Szostak, Experimental Models of Primitive Cellular Compartments: Encapsulation, Growth, and Division, Science, 302 (2003): 618-622.
[3] Peter Walde, Roger Wick, M. Fresta, A. Mangone, P.L. Luisi, J. 1994. Autopoietic Self-Reproduction of Fatty Acid Vesicles. J. Am. Chem. Soc. 116: 11649-11654.
[4] I.A. Chen, R. Roberts, and Jack Szostak. The Emergence of Competition between Model Protocells. Science. 305 (2004):1474-76.
[5] IA Chen and Jack Szostak. 2004. Membrane Growth can Generate a Transmembrane pH Gradient in Fatty Acid Vesicles. Proc Natl Acad Sci. 101 (2004) no. 21: 7965-70.
[6] Zwicker, David, Rabea Seyboldt, Christoph A. Weber, Anthony A. Hyman, and Frank Jülicher. "Growth and Division of Active Droplets: A Model for Protocells." arXiv preprint arXiv:1603.01571 (2016).
[7] Engelhart, Aaron E., Katarzyna P. Adamala, and Jack W. Szostak. "A simple physical mechanism enables homeostasis in primitive cells." Nature chemistry (2016).