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Selection for Replicases in Protocells
PMCID: PMC3649988This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
A stochastic model of catalytic reaction networks in protocells
Protocells are supposed to have played a key role in the self-organizing
processes leading to the emergence of life. Existing models either (i) describe
protocell architecture and dynamics, given the existence of sets of
collectively self-replicating molecules for granted, or (ii) describe the
emergence of the aforementioned sets from an ensemble of random molecules in a
simple experimental setting (e.g. a closed system or a steady-state flow
reactor) that does not properly describe a protocell. In this paper we present
a model that goes beyond these limitations by describing the dynamics of sets
of replicating molecules within a lipid vesicle. We adopt the simplest possible
protocell architecture, by considering a semi-permeable membrane that selects
the molecular types that are allowed to enter or exit the protocell and by
assuming that the reactions take place in the aqueous phase in the internal
compartment. As a first approximation, we ignore the protocell growth and
division dynamics. The behavior of catalytic reaction networks is then
simulated by means of a stochastic model that accounts for the creation and the
extinction of species and reactions. While this is not yet an exhaustive
protocell model, it already provides clues regarding some processes that are
relevant for understanding the conditions that can enable a population of
protocells to undergo evolution and selection.Comment: 20 pages, 5 figure
Effect of migration in a diffusion model for template coexistence in protocells
The compartmentalization of distinct templates in protocells and the exchange
of templates between them (migration) are key elements of a modern scenario for
prebiotic evolution. Here we use the diffusion approximation of population
genetics to study analytically the steady-state properties of such prebiotic
scenario. The coexistence of distinct template types inside a protocell is
achieved by a selective pressure at the protocell level (group selection)
favoring protocells with a mixed template composition. In the degenerate case,
where the templates have the same replication rate, we find that a vanishingly
small migration rate suffices to eliminate the segregation effect of random
drift and so to promote coexistence. In the non-degenerate case, a small
migration rate greatly boosts coexistence as compared with the situation where
there is no migration. However, increase of the migration rate beyond a
critical value leads to the complete dominance of the more efficient template
type (homogeneous regime). In this case, we find a continuous phase transition
separating the homogeneous and the coexistence regimes, with the order
parameter vanishing linearly with the distance to the transition point
Preliminary steps toward artificial protocell computation
Protocells are hypothesised as a transitional phase in the origin of life, prior to the evolution of fully functional prokaryotic cells. The work reported here is being done in the context of the PACE project, which is investigating the fabrication of artificial protocells de novo. We consider here the important open question of whether or how articifial protocells (if or when they are successfully
fabricated) might be applied as “computing” devices—what sort of computing might they be suitable for, and how might they be “programmed”? We also present some preliminary analysis of a crude model of such “evolutionary protocell computation”
Nanoporous silica-based protocells at multiple scales for designs of life and nanomedicine.
Various protocell models have been constructed de novo with the bottom-up approach. Here we describe a silica-based protocell composed of a nanoporous amorphous silica core encapsulated within a lipid bilayer built by self-assembly that provides for independent definition of cell interior and the surface membrane. In this review, we will first describe the essential features of this architecture and then summarize the current development of silica-based protocells at both micro- and nanoscale with diverse functionalities. As the structure of the silica is relatively static, silica-core protocells do not have the ability to change shape, but their interior structure provides a highly crowded and, in some cases, authentic scaffold upon which biomolecular components and systems could be reconstituted. In basic research, the larger protocells based on precise silica replicas of cells could be developed into geometrically realistic bioreactor platforms to enable cellular functions like coupled biochemical reactions, while in translational research smaller protocells based on mesoporous silica nanoparticles are being developed for targeted nanomedicine. Ultimately we see two different motivations for protocell research and development: (1) to emulate life in order to understand it; and (2) to use biomimicry to engineer desired cellular interactions
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The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.
Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes
A model of protocell based on the introduction of a semi-permeable membrane in a stochastic model of catalytic reaction networks
In this work we introduce some preliminary analyses on the role of a
semi-permeable membrane in the dynamics of a stochastic model of catalytic
reaction sets (CRSs) of molecules. The results of the simulations performed on
ensembles of randomly generated reaction schemes highlight remarkable
differences between this very simple protocell description model and the
classical case of the continuous stirred-tank reactor (CSTR). In particular, in
the CSTR case, distinct simulations with the same reaction scheme reach the
same dynamical equilibrium, whereas, in the protocell case, simulations with
identical reaction schemes can reach very different dynamical states, despite
starting from the same initial conditions.Comment: In Proceedings Wivace 2013, arXiv:1309.712
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