An important question that must be answered if we are to understand life's origin fully is whether the living state arose a priori from pre-existing cellular structures. The alternative is that living molecular systems were first present as solutions or adsorbed films, with cellular life developing only at a later evolutionary stage. If the self-assembly of amphiphilic molecules into membranes preceded the origin of life, it is plausible that the earliest living systems may have had access to encapsulated environments. The following concepts and experimental results support this conjecture.

Bilayers assemble from a variety of amphiphilic compounds.

Although contemporary cell membranes incorporate phospholipids as the primary component of the lipid bilayer, it is not necessary to think that complex lipids were required for early cellular life. In fact, simpler amphiphilic molecules can also assemble into bilayer membranes (1). These include single-chain amphiphiles such as soap molecules, glycerol monooleate, oxidized cholesterol, and even detergents like dodecyl sulfate mixed with dodecyl alcohol. It seems likely that primitive cells incorporated lipid-like molecules from the environment, almost as a nutrient, rather than undertaking the more difficult process of synthesizing complex lipids de novo.

Amphiphilic molecules are present in carbonaceous meteorites.

The presence of amino acids in carbonaceous meteorites supports the possibility that amino acids were available in the prebiotic environment. Amphiphilic molecules have also been demonstrated in such meteorites and furthermore have the ability to self-assemble into barrier membranes (2, 3). This observation suggests that amphiphiles were present on the early Earth and available for incorporation into boundary membranes of primitive cellular organisms.

Bilayer permeability strongly depends on chain length of the component amphiphilic molecules.

We tend to think of the lipid bilayer as being a nearly impenetrable barrier to ionic solutes and other large, polar molecules. This leads to a conundrum when we try to imagine how early forms of cellular life could have functioned in the absence of highly evolved transport enzymes that translocate ionic nutrients and metabolites across the bilayer barrier. It is true that lipid bilayers of contemporary cell membranes present a significant permeability barrier that is necessary for normal cell functions, particularly those related to bioenergetics of ion transport and chemiosmotic ATP synthesis. However, recent results show that shortening lipid chain length from 18 to 14 carbons increases the permeation of ionic solutes by several orders of magnitude (4). This level of permeability is sufficient to encapsulate large molecules such as proteins and polynucleotides, yet still allow external substrate to reach an encapsulated enzyme (5). It follows that early cell membranes could have been composed of shorter chain lipids that provided access to nutrients for macromolecules undergoing growth and replication in an encapsulated microenvironment.

Macromolecules can be encapsulated in bilayer vesicles under simulated prebiotic conditions.

Another conceptual problem has been to imagine how vesicular lipid bilayers could capture macromolecules, given that the bilayer must present a nearly impenetrable barrier if the macromolecules are to be maintained within the membrane-bounded volume. There is a reasonably straightforward answer to this question. If dispersed lipids are first mixed with macromolecules such as proteins or nucleic acids, then subjected to drying and wetting cycles to simulate a tide pool environment, the macromolecules are readily captured in membrane-bounded vesicles (6).

Lipid bilayers grow by addition of amphiphilic compounds present in the bulk phase medium.

It is not sufficient for a primitive cell to replicate its macromolecular components unless the boundary membrane can also increase in area to accommodate the internal growth. Recent experimental results from liposome model systems have provided a useful perspective on primitive membrane growth processes (7).

Encapsulated polymerases can synthesize nucleic acids.

Polynucleotide phosphorylase (5, 8), and the enzymes required for the PCR reaction (9) have now been encapsulated in liposomes and shown to synthesize nucleic acids.

What would be required for the next step, to a true replicating system of encapsulated polynucleotides that can undergo cell-like growth? In concept, the answer is straightforward. Externally added substrates must be supplied to the captured polymerase, and a mechanism for simultaneous addition of membrane components to the vesicles must also be available. Furthermore, there should be a regulatory coupling between growth of the internal molecules and growth of the membrane. Last, protein enzymes cannot be used as catalysts because they are not reproduced in such a system. Instead molecules resembling ribozymes should be components of the system, incorporating both genetic information and the polymerase activity. In practice, there is still no way to deal simultaneously with all of these requirements. However, a few years ago it would have been inconceivable that we would soon reach a point at which intravesicular synthesis of nucleic acids became a reality. It seems likely that a laboratory version of an encapsulated replicating system of molecules capable of growth and perhaps evolution will be achieved in the next decade.

References

1. Hargreaves, W. R., and Deamer, D. W. 1978. Liposomes from ionic single-chain amphiphiles. Biochemistry 17:3759-3768.

2. Deamer, D. W. 1985. Boundary structures are formed by organic components of the Murchison carbonaceous chondrite. Nature 317:792-794.

3. Deamer, D. W., and Pashley, R. M. 1989. Amphiphilic components of carbonaceous meteorites. Orig. Life Evol. Biosphere 19:21-33.

4. Paula, S., Volkov, A. G., Van Hoek, A. N., Haines, T. H., and Deamer, D. W. 1996. Permeation of protons, potassium ions and small polar molecules through phospholipid bilayers as a function of membrane thickness. Biophys. J. 70:339-348.

5. Chakrabarti, A., Breaker, R. R., Joyce, G. F., and Deamer, D. W. 1994. Production of RNA by a polymerase protein encapsulated within phospholipid vesicles. J. Mol. Evol. 39:555-559.

6. Deamer, D. W., and Barchfeld, G. L. 1982. Encapsulation of macromolecules by lipid vesicles under simulated prebiotic conditions. J. Mol. Evol. 18:203-206.

7. Walde, P., Wick, R., Fresta, M., Mangone, A., and Luisi, P. L. 1994a. Autopoietic self-reproduction of fatty acid vesicles. J. Am. Chem. Soc. 116:11649-11654.

8. Walde, P., Goto, A., Monnard, P.-A., Wessicken, M., and Luisi, P. L. 1994b. Oparin's reactions revisited: Enzymatic synthesis of poly(adenylic acid) in micelles and self-reproducing vesicles. J. Am. Chem. Soc. 116:7541-7547.

9. Oberholzer, T., Albrizio, M. and Luisi, P. L. 1995. Polymerase chain reaction in liposomes. Current Biology 2:677-682.

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