A Model of the Protocell

What computer simulations of protocellular functions are relevant? The answer to this question depends upon the conceptual model of the protocell. Indeed, for different models of protocells, different sets of laboratory experiments and computer simulations are significant. To define a model that is consistent with both prebiotic condition and contemporary cellular life we have to address several fundamental questions:

What were the environmental conditions of early Earth? The early Earth between 4.4 and 3.9 Ga was the subject of bombardment by large size impactors (comets, meteorites) which delivered sufficient energy to evaporate early oceans. It is likely that life, even if it had formed during that period, could not have survived these impacts. On the other hand, there is compelling evidence of bacterial life from sediments 3.5-3.57 Ga old [4]. These estimates provide time boundaries for the formation of life.

Besides their detrimental effects, early impacts also benefited the origin of life by delivering water, volatiles and organic molecules to Earth [5]. Volatiles from extraterrestrial sources augmented the Earth's atmosphere, which was mostly composed of N₂, CO₂ and CO but did not contain any significant amounts of O₂. This atmosphere was not very conducive to the formation of compounds considered to be good precursors of biological molecules, such as NH₃ and HCN. In an atmosphere of this composition, the greenhouse effect kept surface temperatures above the current level, over 40^oC and perhaps as high as 80-100^oC [6].

In summary, according to current theories, life formed relatively quickly on geological time scales, perhaps as fast as 10⁵-10⁷ years at elevated temperatures in seawater or at aqueous interfaces and in a neutral or, possibly, reducing atmosphere [7].

Was the formation of cellular boundary structures possible in prebiotic conditions? In analogy with contemporary cells, ancestral cells must have been closed structures with an aqueous interior separated from the environment by walls built of amphiphilic molecules. These molecules were assembled into bilayer membranes such that their polar parts were in contact with water whereas their nonpolar portions were buried in the membrane interior. Such structures have several features that would have been highly desirable in prebiotic conditions. Amphiphilic molecules spontaneously accumulate at water-air and water-oil interfaces and, at sufficient concentrations, self-assemble into boundary structures, called vesicles, by agitation or cycles of wetting and drying [8]. Vesicles can grow and divide by acquiring additional amphiphilic material. The concentration of amphiphilic material, and the self-assembly and stability of vesicles are robust phenomena which occur over a fairly broad range of environmental conditions and molecular compositions.

While efficient synthetic pathways to obtain amphiphilic molecules under prebiotic conditions have not been established (a difficulty common to all cellular components) it has been demonstrated that highly heterogeneous mixtures of amphiphiles extracted from the Murchison meteorite can form vesicles [9]. This points to extraterrestrial infall as one possible source of the membrane-forming material and underscores the potential protobiological significance of vesicles.

What were the functions of protocells? The simplest, ``minimal'' cell [10] must have performed several essential functions, such as (a) capturing and transducing energy, (b) sequestering organic matter and ions from the environment, (c) catalyzing the synthesis of its components from the captured material, (d) protecting organic matter accumulated in its interior from dilution in the surrounding water, and (e) self-replication.

In contemporary cells, enzymatic catalysis and bioenergetics are accomplished mostly by proteins inside the cell or embedded in the cell membrane whereas genetic information is transferred during replication by nucleic acids which, in turn, are synthesized by proteins. The discovery that nucleic acids also possess some catalytic activity led to a hypothesis that the current division of functions between proteins and nucleic acids was preceded by an ``RNA world'' [11]. However, synthetic pathways for nucleic acids are among the most difficult to postulate under protobiological conditions. This raises a distinct possibility that protocells initially represented the ``pre-RNA world'' in which cellular functions were performed, probably with low efficiency and specificity, by simple molecules, including possible precursors to proteins (i.e. peptides) and nucleic acids (see for instance Wächterhäuser [12]). Finding how these functions might have been accomplished and what molecules might have been involved is one of the main challenges in studies of protocellular life.

Where did protocellular functions evolve? Studies of protocellular evolution can be based on two fundamentally different hypotheses. According to one hypothesis, cellular structures and functions evolved simultaneously in the protocell. This can be contrasted with an alternative hypothesis that these structures and functions evolved in different environments, such as mineral surfaces, and were incorporated into vesicles at some later stage of evolution, forming a functioning cell. Intermediate scenarios are also possible -- some functions were always associated with protocells while others initially evolved separately. The two extreme hypotheses can be distinguished by observing that both structures and functions sensitively depend on the molecular environment. For example, contemporary bioenergetics is so closely connected with membranes that it would be difficult to imagine its evolution in a different environment. Conversely, any possible alternative mechanism for acquiring and utilizing energy that might have developed outside the cell would have to remain functioning once encapsulated in the protocell, despite environmental change. This argument favors the hypothesis about cellular evolution of at least some functions. A corollary to this argument is that special attention should be focused on unique properties of protocells that distinguish them from other environments and, in particular, on the role of membranes.