Protocell

A protocell is a self-organized, endogenously ordered, spherical collection of lipids proposed as a rudimentary precursor to cells during the origin of life. A central question in evolution is how simple protocells first arose and how their progeny could diversify, thus enabling the accumulation of novel biological emergences over time. Although a functional protocell has not yet been achieved in a laboratory setting, the goal to understand the process appears well within reach.
A protocell is a pre-cell in abiogenesis, and was a contained system consisting of simple biologically relevant molecules like ribozymes, and encapsulated in a simple membrane structure – isolating the entity from the environment and other individuals – thought to consist of simple fatty acids, mineral structures, or rock-pore structures.

Overview

Compartmentalization was important in the origin of life. Membranes form enclosed compartments that are separate from the external environment, thus providing the cell with functionally specialized aqueous spaces. As the lipid bilayer of membranes is impermeable to most hydrophilic molecules, modern cells have membrane transport-systems that achieve nutrient uptake as well as the export of waste. Prior to the development of these molecular assemblies, protocells likely employed vesicle dynamics that are relevant to cellular functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. On the primitive Earth, numerous chemical reactions of organic compounds produced the ingredients of life. Of these substances, amphiphilic molecules might be the first player in the evolution from molecular assembly to cellular life. Vesicle dynamics could progress towards protocells with the development of self-replication coupled with early metabolism. It is possible that protocells might have had a primitive metabolic system at alkaline hydrothermal vents or other geological environments like impact crater lakes from meteorites, which are known to be composed of elements found in the Wood-Ljungdahl pathway.
Another conceptual model of a protocell relates to the term "chemoton" which refers to the fundamental unit of life introduced by Hungarian theoretical biologist Tibor Gánti. It is the oldest known computational abstract of a protocell. Gánti conceived the basic idea in 1952 and formulated the concept in 1971 in his book The Principles of Life. He surmised the chemoton as the original ancestor of all organisms, or the last universal common ancestor.
The basic assumption of the chemoton model is that life should fundamentally and essentially have three properties: metabolism, self-replication, and a bilipid membrane. The metabolic and replication functions together form an autocatalytic subsystem necessary for the basic functions of life, and a membrane encloses this subsystem to separate it from the surrounding environment. Therefore, any system having such properties may be regarded as alive, and will contain self-sustaining cellular information that is subject to natural selection. Some consider this model a significant contribution to origin of life as it provides a philosophy of evolutionary units.

Selectivity for compartmentalization

Self-assembled vesicles are essential components of primitive cells. The second law of thermodynamics requires that the universe becomes increasingly disordered, yet life is distinguished by its great degree of organization. Therefore, a boundary is needed to separate life processes from non-living matter. This fundamental necessity is underpinned by the universality of the cell membrane which is the only cellular structure found in all organisms on Earth.
In the aqueous environment in which all known cells function, a non-aqueous barrier is required to surround a cell and separate it from its surroundings. This non-aqueous membrane establishes a barrier to free diffusion, allowing for regulation of the internal environment within the barrier. The necessity of thermodynamically isolating a subsystem is an irreducible condition of life. In modern biology, such isolation is ordinarily accomplished by amphiphilic bilayers of a thickness of around 10⁻⁸ meters.
Researchers including Irene A. Chen and Jack W. Szostak have demonstrated that simple physicochemical properties of elementary protocells can give rise to simpler conceptual analogues of essential cellular behaviors, including primitive forms of Darwinian competition and energy storage. Such cooperative interactions between the membrane and encapsulated contents could greatly simplify the transition from replicating molecules to true cells. Competition for membrane molecules would favor stabilized membranes, suggesting a selective advantage for the evolution of cross-linked fatty acids and even the phospholipids of today. This micro-encapsulation allowed for metabolism within the membrane, exchange of small molecules and prevention of passage of large substances across it. The main advantages of encapsulation include increased solubility of the cargo and creating energy in the form of chemical gradients. Energy is thus often said to be stored by cells in molecular structures such as carbohydrates, lipids, and proteins, which release energy when chemically combined with oxygen during cellular respiration.

Vesicles, micelles and membranes

When phospholipids or simple lipids like fatty acids are placed in water, the molecules spontaneously arrange such that the hydrophobic tails are shielded from the water, resulting in the formation of membrane structures such as bilayers, vesicles, and micelles. In modern cells, vesicles are involved in metabolism, transport, buoyancy control, and enzyme storage. They can also act as natural chemical reaction chambers. A typical vesicle or micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle center. This phase is caused by the packing behavior of single-tail lipids in a bilayer. Although the spontaneous self-assembly process that form lipid monolayer vesicles and micelles in nature resemble the kinds of primordial vesicles or protocells that might have existed at the beginning of evolution, they are not as sophisticated as the bilayer membranes of today's living organisms. However, in a prebiotic context, electrostatic interactions induced by short, positively charged, hydrophobic peptides containing seven amino acids in length or fewer, can attach RNA to a vesicle membrane, the basic cell membrane.
Rather than being made up of phospholipids, early membranes may have formed from monolayers or bilayers of simple fatty acids, which may have formed more readily in a prebiotic environment. Fatty acids have been synthesized in laboratories under a variety of prebiotic conditions and have been found on meteorites, suggesting their natural synthesis in nature. Oleic acid vesicles represent good models of membrane protocells.
Põldsalu et al. suggested that the formation of model protocells from multilamellar lipid reservoirs starting from mixed amphiphiles is a plausible scenario for the emergence of the first cells.
Cohen et al. suggested that plausible prebiotic production of fatty acids — leading to the development of early protocell membranes — is enriched on metal-rich mineral surfaces, possibly from impact craters, increasing the prebiotic environmental mass of lipids by 10² times. They evaluated three different possible synthesis pathways of fatty acids in the Hadean, and found that these metal surfaces could produce 10¹¹ - 10¹⁵ kg of 6-18 carbon fatty acids. Of these products, the 8-18C fatty acids are compatible with membrane formation. They also proposed that alternative amphiphiles like alcohols are co-synthesized with fatty acid, and can help improve membrane stability. However, despite this production, the authors stated that net fatty acid synthesis would not yield sufficient concentrations for spontaneous membrane formation without significant evaporation of Earth's aqueous environments.
Cho et al. showed that cysteine can generate membrane vesicles characteristic of protocells by spontaneously reacting with two short-chain thioesters to form diacyl lipids. That same year, Pulletikurti et al. showed a potential mechanism for the transition from fatty-acid-based to phospholipid vesicles using cyclic-phospholipids formed from fatty acids and glycerol. Also that year, while replicating the Miller-Urey experiment, Jenewein et al. found that silica in the presence of water induces the formation of biomorphic protocells.

Membrane transport

For cellular organisms, the transport of specific molecules across compartmentalizing membrane barriers is essential in order to exchange content with their environment and with other individuals. For example, content exchange between individuals enables the exchange of genes between individuals, an important factor in the evolution of cellular life. While modern cells can rely on complicated protein machineries to catalyze these crucial processes, protocells must have accomplished this using more simple mechanisms.
Protocells composed of fatty acids would have been able to easily exchange small molecules and ions with their environment. Modern phospholipid bilayer cell membranes exhibit low permeability, but contain complex molecular assemblies which both actively and passively transport relevant molecules across the membrane in a highly specific manner. In the absence of these complex assemblies, simple fatty acid based protocell membranes would be more permeable and allow for greater non-specific transport across membranes. Molecules that would be highly permeable across protocell membranes include nucleoside monophosphate, nucleoside diphosphate, and nucleoside triphosphate, and may withstand millimolar concentrations of Mg²⁺. Osmotic pressure can also play a significant role regarding this passive membrane transport.
Environmental effects have been suggested to trigger conditions under which a transport of larger molecules, such as DNA and RNA, across the membranes of protocells is possible. For example, it has been proposed that electroporation resulting from lightning strikes could enable such transport. Electroporation is the rapid increase in bilayer permeability induced by the application of a large artificial electric field across the membrane. During electroporation, the lipid molecules in the membrane shift position, opening up a pore that acts as a conductive pathway through which hydrophobic molecules like nucleic acids can pass the lipid bilayer. A similar transfer of content across protocells and with the surrounding solution can be caused by freezing and subsequent thawing. This could, for instance, occur in an environment in which day and night cycles cause recurrent freezing. Laboratory experiments have shown that such conditions allow an exchange of genetic information between populations of protocells. This can be explained by the fact that membranes are highly permeable at temperatures slightly below their phase transition temperature. If this point is reached during the freeze-thaw cycle, even large and highly charged molecules can temporarily pass the protocell membrane.
Some molecules or particles are too large or too hydrophilic to pass through a lipid bilayer even under these conditions, but can be moved across the membrane through fusion or budding of vesicles, events which have also been observed for freeze-thaw cycles. This may eventually have led to mechanisms that facilitate movement of molecules to the inside of the protocell or to release its contents into the extracellular space.