5.5. Protocell assembly#
Professor: Claudia Bonfio (Biochemistry)
Learning objectives:
To understand what a primitive cell is
To understand how a primitive cell could have assembled from the building blocks of life
Introduction#
The emergence of life from non-living chemistry remains one of the greatest questions in science. A crucial step in this transition was the formation of protocells—primitive cell-like structures that could encapsulate and organize biochemical reactions. Protocells serve as models for understanding how the first living systems could have originated and evolved. Their defining features include a compartment (such as a membrane or droplet), a means of energy acquisition, and the ability to grow, divide, and undergo selection.
This lecture explores two major types of protocellular compartments—lipid membranes and coacervates—and discusses how these structures may have contributed to the emergence of functional protocells by incorporating prebiotic chemical reactions.
What is a protocell?#
A protocell is a primitive, self-assembled structure that mimics some of the essential properties of living cells. Unlike modern cells, protocells likely lacked complex molecular machinery, but they provided a way to concentrate and organize prebiotic molecules, facilitating the emergence of life-like behaviors such as metabolism and information storage.
While there are multiple hypotheses about the earliest protocells, two primary models have gained experimental and theoretical support:
Membrane-bound protocells – lipid vesicles, often comprising fatty acids or phospholipids, that host chemical reactions.
Membraneless coacervates – phase-separated droplets, often formed by interactions between charged biomolecules, that host chemical reactions.
Each model offers distinct advantages, and it is possible that both played a role in early life.
Lipid membranes: The first cellular boundaries?#
Fatty Acid Vesicles as Protocells#
Modern cells are defined by their phospholipid membranes, which create a stable, semi-permeable barrier. Instead, protocells may have relied on simpler fatty acids, which were likely available through prebiotic chemistry or delivered by meteorites.
Fatty acids spontaneously self-assemble into bilayer vesicles in water, forming compartments that can grow and divide in response to environmental changes. Experimental work, particularly from the Szostak Lab, has shown that these fatty acid vesicles can:
Form under plausible prebiotic conditions.
Grow by incorporating additional fatty acids from the environment.
Divide when subjected to gentle agitation or osmotic stress.
Allow small molecules (such as nucleotides) to enter without requiring complex transport proteins.
These properties make fatty acid vesicles strong candidates for early protocell membranes, capable of creating a protected environment where chemical evolution could take place.
Prebiotic Chemistry Within Membranes#
A key challenge in protocell research is integrating chemical reactions within compartments. Studies suggest that prebiotic RNA polymerization can occur inside fatty acid vesicles, supporting the idea that early genetic systems could have operated within primitive membranes. Furthermore, encapsulated ribozymes—RNA molecules with catalytic activity—have been shown to remain functional, hinting that protocells could have supported early enzymatic reactions.
Another important finding from the Szostak group is that protocells with fatty acid membranes can interact with simple peptides, which may have stabilized membranes and enhanced protocell functionality. This provides a potential link between early cells and the emergence of primitive proteins.
Coacervates: Membraneless Protocells#
What Are Coacervates?#
Coacervates are membraneless droplets that form through phase separation. Complex coacervates form when charged polymers, such as RNA and peptides, spontaneously aggregate in solution. Unlike lipid vesicles, coacervates do not have a defined boundary, but they can still concentrate and organize biomolecules, acting as microreactors for prebiotic chemistry.
The concept of coacervates as protocells dates back to Alexander Oparin’s early theories on the origin of life. Recent experiments from the Keating and Spruijt groups have demonstrated that coacervates can:
Selectively concentrate nucleotides and amino acids, increasing reaction efficiency.
Provide an environment that protects RNA from degradation.
Support primitive catalytic reactions, such as RNA polymerization.
Membranes vs. Coacervates: A Competition or a Collaboration?#
Lipid vesicles and coacervates offer distinct advantages. While vesicles provide a stable compartment, coacervates offer a dynamic environment where molecules can diffuse in and out freely. Some researchers propose that early protocells may have utilized hybrid systems, where coacervates formed inside lipid vesicles, combining the strengths of both models.
For example, recent work from the Keating and Spruijt groups suggests that lipid-coated coacervates could provide selective permeability, allowing protocells to retain beneficial molecules while excluding harmful ones. This hybrid approach could have played a role in the transition from simple chemical systems to more robust, evolving protocells.
Towards Functional Protocells: The Role of Prebiotic Chemistry#
A critical goal in protocell research is to integrate genetic, metabolic, and structural components into a single system. Several key advances have demonstrated how protocells could have become more life-like:
RNA replication in vesicles and coacervates: Several studies have shown that encapsulated RNA can undergo non-enzymatic polymerization, a crucial step toward heredity.
Catalytic coacervates: Experiments suggest that coacervates enriched with ribozymes can drive simple biochemical reactions.
Growth and division: Protocells must be able to grow and divide to evolve. Fatty acid vesicles can grow by incorporating external lipids and divide through simple mechanical forces, mimicking cellular reproduction.
By combining these findings, researchers are getting closer to understanding how primitive compartments could have led to the emergence of the first living cells.
Conclusion#
The assembly of protocells was a crucial step in the origin of life. While lipid vesicles provided stable compartments that could encapsulate and protect genetic material, coacervates offered a dynamic environment for molecular interactions. The interplay between these two models, along with the integration of prebiotic chemical reactions, represents a key area of research in understanding life’s origins.
Ongoing work continues to refine protocell models, bringing us closer to answering fundamental questions about how life emerged on Earth—and possibly elsewhere in the universe.