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The University of Southampton

Research project: Attard: Mapping the effects of molecular crowding and reduced dimensionality of complex reaction networks

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The aims of this research programme are to produce an atlas of the Belouzov-Zhabotinsky reaction for different degrees of molecular crowding, and to develop an understanding of how crowding and reduced dimensionality affect model biochemical reaction networks that also lead to morphological changes over length scales of several hundred nm.key words: oscillating reaction, complexity, reaction networks, self-assembly, self-organisation, reduced dimensionality, molecular crowding, reaction-diffusion systems

While the crowded nature of the intracellular environment has been recognised for more that 25 years, it is only relatively recently that its impact on the properties and function of intracellular macromolecules has become the subject of systematic research. In part this focus has been motivated by the need for realistic estimates of protein functional parameters that can be used in 'whole cell' mathematical/computational models. The issue of how molecular crowding and diffusion in reduced dimensionality environments affects chemical reactivity is also of wider and fundamental scientific interest. Our research addresses two issues. The first is the current lack of widely accepted systems and protocols that provide good model representations of the intracellular milieu that can be used to, for example, measure realistic enzyme kinetic parameters. We are conducting a systematic screening of a range of molecular crowding agents and how they affect the kinetics of a variety of enzyme catalysed reactions in order to identify ‘standard’ conditions and protocols that are good models of the intracellular environment. The second issue we are addressing is more fundamental in nature, and concerns the effect of crowding and reduced dimensionality on complex reaction/diffusion systems. We are using the well-established Belousov-Zhabotinsky oscillating reaction to create an atlas that maps the relationships between process parameters (e.g. concentrations of species, temperature, concentration of crowding agent) and oscillation frequencies/amplitudes in well-stirred mixtures, as well pattern formation in diffusion/convection preparations. The atlas will then be extended to investigate the effects of the reaction occurring in nanostructured environments (e.g. in gels or in lyotropic liquid crystalline phases). In this way we plan to build up an understanding of how a complex but tractable reaction network, with a wide separation of reaction rates, behaves as the components become more crowded and/or the dimensionality of the space changes. We plan to use these insights to study an synthetic biochemical network that involves the synthesis of lipids in order to determine how the reaction/diffusion effects in crowded systems can be coupled with changes that cause dynamic morphological changes over length scales of several hundred nanometers. This research is being carried out in collaboration with Klaus-Peter Zauner (Electronics & Computer Science), Marcus Dymond (Pharmacy & Biomolecular Sciences, University of Brighton), Jayne Lawrence (Pharmacy, Kings College London), Adam Squires (Chemistry, University of Reading), Yuru Deng (Wenzhou Institute of Biomaterials and Engineering) and Tommy Nylander (Chemistry, Lund University).

Schematic showing links between molecular crowding, reduced dimensionality and nanostructured phases.
click on image to enlarge

Related research groups

Chemical Biology, Diagnostics and Therapeutics
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