Modelling compartmentalization towards elucidation and engineering of spatial organization in biochemical pathways
Author(s)
Menon, G
Okeke, C
Krishnan, J
Type
Journal Article
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.
Date Issued
2017-09-21
Date Acceptance
2017-08-08
Citation
Scientific Reports, 2017, 7
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
7
Copyright Statement
© The Author(s) 2017. his article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-
ative Commons license, and indicate if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not per-
mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit
http://creativecommons.org/licenses/by/4.0/
.
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-
ative Commons license, and indicate if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not per-
mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit
http://creativecommons.org/licenses/by/4.0/
.
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
ARTIFICIAL CELLS
GENE-EXPRESSION
SUBCELLULAR COMPARTMENTALIZATION
SIGNAL-TRANSDUCTION
METABOLIC PATHWAYS
MICROCOMPARTMENTS
PHOSPHORYLATION
MICRODOMAINS
STRATEGIES
ORGANELLES
Publication Status
Published
Article Number
12057