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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 the inert compound [Iex]. Vesicle radius (left upper plot), division time (right upper plot), overall internal concentrations of RNA strands (left lower plot) and genome composition percentage (right lower plot) were determined after 20 generations.
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Figure 3: Dependence of the Ribocell stationary regime on the external concentration of the inert compound [Iex]. Vesicle radius (left upper plot), division time (right upper plot), overall internal concentrations of RNA strands (left lower plot) and genome composition percentage (right lower plot) were determined after 20 generations.

Mentions: As first, the dependence of Ribocell state on overall external concentration CTE is analyzed at the stationary regime, reached after 20 generations. Since [Pex] = [Nex] = 5.0·10-4M, the overall external concentration can be approximated to CTE≈[Iex]. The upper plots in Figure 3 show that when the overall external concentration [Iex] increases, then the Ribocell radius ρ20 decreases, while the life cycle Δt20 rises. Thus, vesicles become smaller and more dormant as the overall external concentration rises. This can be ascribed to the mechanism of synchronization itself and is in agreement with what we reported in a recent work (unpublished paper) where an inverse dependence of the vesicle steady size on overall external concentration was explicitly derived from the general stationary condition γ = 1. On the other hand, the observed increase in Ribocell life time is a direct consequence of the reduction in size, since a smaller membrane surface decreases the transport efficiency of substrates (lipid precursor and nucleotides) from outside. As a consequence of this, all metabolic processes slow down since they are sustained by the transport of external substrates. These two effects, i.e. the increase in lifetime and the slowdown of the metabolism, determine the linear rise in concentration of the overall genetic material, see the lower left plot of Figure 3. At the steady regime, the genome composition is almost independent of [Iex], as shown by the lower right plot of


Stochastic simulations of minimal cells: the Ribocell model.

Mavelli F - BMC Bioinformatics (2012)

Dependence of the Ribocell stationary regime on the external concentration of the inert compound [Iex]. Vesicle radius (left upper plot), division time (right upper plot), overall internal concentrations of RNA strands (left lower plot) and genome composition percentage (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 3: Dependence of the Ribocell stationary regime on the external concentration of the inert compound [Iex]. Vesicle radius (left upper plot), division time (right upper plot), overall internal concentrations of RNA strands (left lower plot) and genome composition percentage (right lower plot) were determined after 20 generations.
Mentions: As first, the dependence of Ribocell state on overall external concentration CTE is analyzed at the stationary regime, reached after 20 generations. Since [Pex] = [Nex] = 5.0·10-4M, the overall external concentration can be approximated to CTE≈[Iex]. The upper plots in Figure 3 show that when the overall external concentration [Iex] increases, then the Ribocell radius ρ20 decreases, while the life cycle Δt20 rises. Thus, vesicles become smaller and more dormant as the overall external concentration rises. This can be ascribed to the mechanism of synchronization itself and is in agreement with what we reported in a recent work (unpublished paper) where an inverse dependence of the vesicle steady size on overall external concentration was explicitly derived from the general stationary condition γ = 1. On the other hand, the observed increase in Ribocell life time is a direct consequence of the reduction in size, since a smaller membrane surface decreases the transport efficiency of substrates (lipid precursor and nucleotides) from outside. As a consequence of this, all metabolic processes slow down since they are sustained by the transport of external substrates. These two effects, i.e. the increase in lifetime and the slowdown of the metabolism, determine the linear rise in concentration of the overall genetic material, see the lower left plot of Figure 3. At the steady regime, the genome composition is almost independent of [Iex], as shown by the lower right plot of

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