Abstract
Compartmentalization is a fundamental ingredient, central to the functioning of biological systems at multiple levels. At the cellular level, compartmentalization is a key aspect of the functioning of biochemical pathways and an important element used in evolution. It is also being exploited in multiple contexts in synthetic biology. Accurate understanding of the role of compartments and designing compartmentalized systems needs reliable modelling/systems frameworks. We examine a series of building blocks of signalling and metabolic pathways with compartmental organization. We systematically analyze when compartmental ODE models can be used in these contexts, by comparing these models with detailed reaction-transport models, and establishing a correspondence between the two. We build on this to examine additional complexities associated with these pathways, and also examine sample problems in the engineering of these pathways. Our results indicate under which conditions compartmental models can and cannot be used, why this is the case, and what augmentations are needed to make them reliable and predictive. We also uncover other hidden consequences of employing compartmental models in these contexts. Or results contribute a number of insights relevant to the modelling, elucidation, and engineering of biochemical pathways with compartmentalization, at the core of systems and synthetic biology.
Highlights
Information processing, and most vital aspects of cellular life are underpinned by complex and sophisticated protein and genetic networks
It is well known that spatial organization of pathways, with components distributed between different locations: the membrane, the cytoplasm, and membrane bound compartments such as organelles, vesicles, and the nucleus, is ubiquitous in both signaling4–7and metabolic processes[8,9]
For any biochemical pathway that we study, the kinetics and compartment sizes are common to both types of models
Summary
Information processing, and most vital aspects of cellular life are underpinned by complex and sophisticated protein and genetic networks. Even bacterial cells, which lack organelles, exhibit precise spatial organization of processes[10,11], including compartmentalization of metabolic pathways[12]. While this spatial organization is generally recognized, its effect on the functioning of the pathways is generally not well explored. It is clear that there is a certain degree of localization/compartmentalization in bacteria, but that this is very much greater in eukaryotes How this new feature is exploited in different cell types and to what end is still an open question. There are experimental studies which explore the origins of life, using vesicles to compartmentalize reactions and thereby capture the essential features of proto-cells
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