Problems During Cell Cycle in Artificial Cell Modeling

Abstract

In the last decades, progresses were made in the insight of microbiological processes. The mathematical description of biological processes by system biological models has been widely accepted as useful for a deepened understanding of existing biological systems. This development paves the way towards a systematic construction of artificial biological systems with tailored properties, which is the topic of synthetic biology. Our aim is to evolve an artificial cell model consisting of functional biological devices like genome, transcriptome, proteome and metabolome. Although various mathematical models have been proposed to describe an artificial cell (Ganti, 2003; Novak and Tyson, 2008), there is a need for further theoretical analysis and mathematical modeling for a proper understanding of interactions between the functional devices. Most of the artificial cell models may be structured into three functional devices representing a container forming the boundary of the cell, a metabolism generating the building blocks of the cell, and a programming part containing genetic information and regulating the processes inside the cell (Rasmussen et al., 2003). Self-replication of an artificial cell requires a synchronization of those three functional devices in such a way that at the end of the cell cycle the material in each of the devices has at least doubled. A key problem, which is addressed in this work, seems to be how to find a structure that guarantees this synchronization in a robust way, i.e. more or less independent of the kinetic parameter values. The need for the biological robustness is justified by the aim to be able to deal with perturbations. As a starting point, we consider the Chemoton model described by T. Ganti (Ganti, 2003). The Chemoton consists of three self-reproducing functional devices: the autocatalytic chemical cycle representing the metabolism, the template polymerization subsystem serving as an information carrier and the membrane representing a container which grows proportional to the polymerization process. Although the Chemoton model is able to show self-sustained oscillations, these oscillations are not necessarily synchronized with cell growth. To achieve this, a careful tuning of the kinetic parameters is required. The question is, if there is a model structure related to the Chemoton approach that possesses an inherent mechanism guaranteeing the synchronization of metabolism, program and container for a wide range of kinetic parameter values. As a first step towards such a model structure, we combine the devices of the Chemoton model with the less complex structure of minimal cascade model for the mitotic oscillator described by Goldbeter (1991). The schematic representation of our artificial cell model is shown in Figure 1.