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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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The Ribocell internal metabolism. (1) Reversible RNA strand association, (2) catalyzed template transcription (S = RP, cRP, RL, and cRL,) (3) lipid synthesis.
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Figure 1: The Ribocell internal metabolism. (1) Reversible RNA strand association, (2) catalyzed template transcription (S = RP, cRP, RL, and cRL,) (3) lipid synthesis.

Mentions: In previous papers [15,16], we have presented an in silico implementation of the Ribocell based on the internal metabolism reported in Figure 1 and on the recently introduced self-replicating lipid vesicle model [17]. By means of a deterministic analysis, we showed that if the kinetic constant for lipid formation kL is in the range: 1.7·103s-1M-1≤kL≤1.7·105s-1M-1 then synchronization between vesicle reproduction and genome replication can spontaneously emerge under the model assumptions and kinetic parameters reported in Table 1. Deterministic calculations were performed for two ribozymes 20 bases long and showed that the Ribocell reaches a stationary growth and division regime, where the cell size remains constant after each division along with the amount of genetic materials. Although the observed cell life time stabilizes after the first 10 generations, it remains very high, at over 80 days for all the kLvalues in the synchronization range, making the Ribocell very hard to implement and study experimentally.


Stochastic simulations of minimal cells: the Ribocell model.

Mavelli F - BMC Bioinformatics (2012)

The Ribocell internal metabolism. (1) Reversible RNA strand association, (2) catalyzed template transcription (S = RP, cRP, RL, and cRL,) (3) lipid synthesis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The Ribocell internal metabolism. (1) Reversible RNA strand association, (2) catalyzed template transcription (S = RP, cRP, RL, and cRL,) (3) lipid synthesis.
Mentions: In previous papers [15,16], we have presented an in silico implementation of the Ribocell based on the internal metabolism reported in Figure 1 and on the recently introduced self-replicating lipid vesicle model [17]. By means of a deterministic analysis, we showed that if the kinetic constant for lipid formation kL is in the range: 1.7·103s-1M-1≤kL≤1.7·105s-1M-1 then synchronization between vesicle reproduction and genome replication can spontaneously emerge under the model assumptions and kinetic parameters reported in Table 1. Deterministic calculations were performed for two ribozymes 20 bases long and showed that the Ribocell reaches a stationary growth and division regime, where the cell size remains constant after each division along with the amount of genetic materials. Although the observed cell life time stabilizes after the first 10 generations, it remains very high, at over 80 days for all the kLvalues in the synchronization range, making the Ribocell very hard to implement and study experimentally.

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