Statistical Physics of Active Enzyme Suspensions

Lead Research Organisation: University of Oxford
Department Name: Oxford Physics

Abstract

Understanding the dynamics of biomolecules is crucial if we are to fully appreciate and potentially harness their functionalities in the search for biocompatible micro- and nanomachines. However, there are currently many obstacles obscuring the path to a complete description at the fundamental level that would allow for the design and fabrication of such machines. The intrigue and complication is increased by the variety of biomolecular species, meaning that there are many possible applications, but also that their physical properties do not obviously fit into one universality class. For example, a variety of propulsion mechanisms have been observed and predicted for microscopic swimmers. Enzymes have received a lot attention for their ability to perform very specific functions at nanoscales under conditions dominated by thermal fluctuations and viscous hydrodynamics. Recently, the question of the effect of catalytic activity of enzymes on their diffusion properties has been studied. Experiments with dilute solutions of enzyme molecules which catalyse exothermic reactions and typically have high catalytic rates have revealed that their diffusion is substantially enhanced in a way that is dependent on the substrate concentration when they are catalytically active. Accordingly, there have been theoretical investigations into the underlying mechanism of the phenomenon, such as explanations founded on the exothermicity and fast rate of catalysis of the chemical cycle of the enzyme. The effect of hydrodynamic coupling of enzyme molecules to their environment has also been studied. All of the theories proposed so far relied on the idea that the catalytic cycle is out of equilibrium, or fail to accurately describe the experimental evidence without very specific atypical assumptions. Furthermore, the observation appears to be generic: Recent experiments have demonstrated enhanced diffusion in the endothermic and slow enzyme aldolase. The phenomenon is observed for a wide range of enzymes with very different chemical properties, which were not captured by existing theoretical frameworks for enhanced diffusion. Therefore, we investigate a new theoretical approach to the understanding of this physical phenomenon, capable of replicating all of the experimental evidence. With this, we hope to propose a new universal theory for enhanced diffusion of enzyme molecules which is independent of their non-physical properties.
This project falls within the EPSRC physical sciences grand challenges of Emergence and Physics Far from Equilibrium, Nanoscale Design of Functional Materials, and Understanding the Physics of Life.

Publications

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Adeleke-Larodo T (2019) Chemical and hydrodynamic alignment of an enzyme. in The Journal of chemical physics

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Adeleke-Larodo T (2019) Fluctuation-induced hydrodynamic coupling in an asymmetric, anisotropic dumbbell. in The European physical journal. E, Soft matter

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Agudo-Canalejo J (2018) Enhanced Diffusion and Chemotaxis at the Nanoscale. in Accounts of chemical research

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509711/1 01/10/2016 30/09/2021
1964308 Studentship EP/N509711/1 01/10/2016 30/09/2019 Tunrayo Adeleke-Larodo
 
Description Biological systems are typically out of thermodynamic equilibrium, and are increasingly being studied in order to develop our understanding of the physics of non-equilibrium systems which are more general. Enzymatic systems are ubiquitous and their catalytic cycles are an apparent example of non-equilibrium phenomena which is commonly studied in statistical physics and non-linear dynamics. Recently, there has been interest in studying the affect of catalysis on the catalysing enzymes, specifically on their dynamics.

We have proposed a minimal model for enzymes which we have successfully used to study the dynamics of a single enzyme molecule under two biologically relevant conditions. So far we have used our model to suggest a new theoretical explanation for the experimentally reported phenomenon of "enhanced-diffusion" in the presence of a uniform distribution of its substrate. Our approach is novel in that it does not rely on any non-equilibrium aspect of the catalytic cycle.

We have also studied the response of a single enzyme molecule to a substrate concentration gradient, where directed stochastic motion, similar to what has been observed in bacteria, has recently been reported. Our model predicts that the enzyme will align parallel or anti-parallel to the field, depending on the sign of the interactions between the enzyme and substrate molecules. In addition to the chemically induced alignment, we have found that an enzyme molecule can also show directed motion is response to gradients in the concentration of the enzyme, due to asymmetry in the geometry of the enzyme which leads to a coupling of its translational and rotational motion.

We expect that the effects we have reported so far will be manifest for a collection of enzymes, and with richer implications. To this end, we have been investigating the possibility of collective phenomena in the non-linear dynamics.
Exploitation Route Our minimal model for enzymes is already being adopted in simulations and other theoretical work by others.
Sectors Other

 
Description Special Grant
Amount £800 (GBP)
Organisation University of Oxford 
Department St John's College Oxford
Sector Academic/University
Country United Kingdom
Start 09/2017 
End 09/2017
 
Description Special Grant
Amount £800 (GBP)
Organisation University of Oxford 
Department St John's College Oxford
Sector Academic/University
Country United Kingdom
Start 09/2018 
End 09/2018
 
Description Travel Grant
Amount € 200 (EUR)
Organisation Technical University of Dresden 
Sector Academic/University
Country Germany
Start 08/2017 
End 08/2017