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Stochastic simulations of minimal cells: the Ribocell model.

Mavelli F - BMC Bioinformatics (2012)

Bottom Line: In particular, the combination of solute compartmentalization, reactivity and stochastic effects has not yet been clarified.This model assumes the existence of two ribozymes, one able to catalyze the conversion of molecular precursors into lipids and the second able to replicate RNA strands.The aim of this contribution is to explore the feasibility of this hypothetical minimal cell.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry Department, University Aldo Moro, Bari, 70125, Italy. mavelli@chimica.uniba.it

ABSTRACT

Background: Over the last two decades, lipid compartments (liposomes, lipid-coated droplets) have been extensively used as in vitro "minimal" cell models. In particular, simple and complex biomolecular reactions have been carried out inside these self-assembled micro- and nano-sized compartments, leading to the synthesis of RNA and functional proteins inside liposomes. Despite this experimental progress, a detailed physical understanding of the underlying dynamics is missing. In particular, the combination of solute compartmentalization, reactivity and stochastic effects has not yet been clarified. A combination of experimental and computational approaches can reveal interesting mechanisms governing the behavior of micro compartmentalized systems, in particular by highlighting the intrinsic stochastic diversity within a population of "synthetic cells".

Methods: In this context, we have developed a computational platform called ENVIRONMENT suitable for studying the stochastic time evolution of reacting lipid compartments. This software - which implements a Gillespie Algorithm - is an improvement over a previous program that simulated the stochastic time evolution of homogeneous, fixed-volume, chemically reacting systems, extending it to more general conditions in which a collection of similar such systems interact and change over the course of time. In particular, our approach is focused on elucidating the role of randomness in the time behavior of chemically reacting lipid compartments, such as micelles, vesicles or micro emulsions, in regimes where random fluctuations due to the stochastic nature of reacting events can lead an open system towards unexpected time evolutions.

Results: This paper analyses the so-called Ribocell (RNA-based cell) model. It consists in a hypothetical minimal cell based on a self-replicating minimum RNA genome coupled with a self-reproducing lipid vesicle compartment. This model assumes the existence of two ribozymes, one able to catalyze the conversion of molecular precursors into lipids and the second able to replicate RNA strands. The aim of this contribution is to explore the feasibility of this hypothetical minimal cell. By deterministic kinetic analysis, the best external conditions to observe synchronization between genome self-replication and vesicle membrane reproduction are determined, while its robustness to random fluctuations is investigated using stochastic simulations, and then discussed.

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Dependence of the Ribocell stationary regime on the external concentration of nucleotides [Nex] and lipid precursor [Pex]. Vesicle radius (upper plot), division time (left lower plot) and logarithm of the overall internal concentrations of RNA strands (right lower plot) were determined after 20 generations.
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Figure 4: Dependence of the Ribocell stationary regime on the external concentration of nucleotides [Nex] and lipid precursor [Pex]. Vesicle radius (upper plot), division time (left lower plot) and logarithm of the overall internal concentrations of RNA strands (right lower plot) were determined after 20 generations.

Mentions: Setting [Iex] = 0.3 M, we study the dependence of the stationary division regime on the external concentration of the substrates: lipid precursor [Pex] and nucleotides. The same concentration value [Nex] is set for the four different nucleotides since they have been assumed to have the same kinetic behavior. The upper plot of Figure 4 shows the opposite effects of [Nex] and [Pex] on the stationary vesicle radius ρ20. Higher [Nex] concentrations speed up genome self-replication with respect to lipid synthesis, accelerating waste production and leading to larger core volumes. Conversely, increasing [Pex] reduces ρ20 since membrane self-reproduction becomes faster. For the same reason, the total concentration of genetic material is increased due to the high concentrations of nucleotides and the low concentrations of the lipid precursor, while, both substrate concentrations decrease cell life time when they are increased, since all the metabolic processes are accelerated. If [Nex] ≥ 0.05 M, the Ribocell undergoes an osmotic burst since volume growth is too fast compared to lipid production for any value of [Pex] in the studied range (see additional file 1).


Stochastic simulations of minimal cells: the Ribocell model.

Mavelli F - BMC Bioinformatics (2012)

Dependence of the Ribocell stationary regime on the external concentration of nucleotides [Nex] and lipid precursor [Pex]. Vesicle radius (upper plot), division time (left lower plot) and logarithm of the overall internal concentrations of RNA strands (right lower plot) were determined after 20 generations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3303737&req=5

Figure 4: Dependence of the Ribocell stationary regime on the external concentration of nucleotides [Nex] and lipid precursor [Pex]. Vesicle radius (upper plot), division time (left lower plot) and logarithm of the overall internal concentrations of RNA strands (right lower plot) were determined after 20 generations.
Mentions: Setting [Iex] = 0.3 M, we study the dependence of the stationary division regime on the external concentration of the substrates: lipid precursor [Pex] and nucleotides. The same concentration value [Nex] is set for the four different nucleotides since they have been assumed to have the same kinetic behavior. The upper plot of Figure 4 shows the opposite effects of [Nex] and [Pex] on the stationary vesicle radius ρ20. Higher [Nex] concentrations speed up genome self-replication with respect to lipid synthesis, accelerating waste production and leading to larger core volumes. Conversely, increasing [Pex] reduces ρ20 since membrane self-reproduction becomes faster. For the same reason, the total concentration of genetic material is increased due to the high concentrations of nucleotides and the low concentrations of the lipid precursor, while, both substrate concentrations decrease cell life time when they are increased, since all the metabolic processes are accelerated. If [Nex] ≥ 0.05 M, the Ribocell undergoes an osmotic burst since volume growth is too fast compared to lipid production for any value of [Pex] in the studied range (see additional file 1).

Bottom Line: In particular, the combination of solute compartmentalization, reactivity and stochastic effects has not yet been clarified.This model assumes the existence of two ribozymes, one able to catalyze the conversion of molecular precursors into lipids and the second able to replicate RNA strands.The aim of this contribution is to explore the feasibility of this hypothetical minimal cell.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry Department, University Aldo Moro, Bari, 70125, Italy. mavelli@chimica.uniba.it

ABSTRACT

Background: Over the last two decades, lipid compartments (liposomes, lipid-coated droplets) have been extensively used as in vitro "minimal" cell models. In particular, simple and complex biomolecular reactions have been carried out inside these self-assembled micro- and nano-sized compartments, leading to the synthesis of RNA and functional proteins inside liposomes. Despite this experimental progress, a detailed physical understanding of the underlying dynamics is missing. In particular, the combination of solute compartmentalization, reactivity and stochastic effects has not yet been clarified. A combination of experimental and computational approaches can reveal interesting mechanisms governing the behavior of micro compartmentalized systems, in particular by highlighting the intrinsic stochastic diversity within a population of "synthetic cells".

Methods: In this context, we have developed a computational platform called ENVIRONMENT suitable for studying the stochastic time evolution of reacting lipid compartments. This software - which implements a Gillespie Algorithm - is an improvement over a previous program that simulated the stochastic time evolution of homogeneous, fixed-volume, chemically reacting systems, extending it to more general conditions in which a collection of similar such systems interact and change over the course of time. In particular, our approach is focused on elucidating the role of randomness in the time behavior of chemically reacting lipid compartments, such as micelles, vesicles or micro emulsions, in regimes where random fluctuations due to the stochastic nature of reacting events can lead an open system towards unexpected time evolutions.

Results: This paper analyses the so-called Ribocell (RNA-based cell) model. It consists in a hypothetical minimal cell based on a self-replicating minimum RNA genome coupled with a self-reproducing lipid vesicle compartment. This model assumes the existence of two ribozymes, one able to catalyze the conversion of molecular precursors into lipids and the second able to replicate RNA strands. The aim of this contribution is to explore the feasibility of this hypothetical minimal cell. By deterministic kinetic analysis, the best external conditions to observe synchronization between genome self-replication and vesicle membrane reproduction are determined, while its robustness to random fluctuations is investigated using stochastic simulations, and then discussed.

Show MeSH
Related in: MedlinePlus