A Chemically Fuelled Self-Replicator

This work reports a system of replicating micelles operating out-of-equilibrium under the continuous supply of a chemical fuel.

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Mar 01, 2019

When we perform a reaction in a closed system, it doesn’t come as a surprise that the system faithfully obeys thermodynamic laws. Reactions drive in the direction of the most stable products and assemblies, which sit undisturbed unless the energy landscape is altered. The molecules and structures of biological systems, however, are a little different. All living systems exist out-of-equilibrium, continuously consuming energy to operate complex biological machinery. Their persistence is no longer determined solely by their thermodynamic stability and, out-of-equilibrium, emergent properties arise that are simply not accessible in a closed system. A classical example of these dynamics can be found in the self-assembly of microtubules, which provide structural integrity to cells and cell division machinery: GTP-tubulin self-assembles into a microtubule structure but, once assembled, is unstable towards hydrolysis. It is only under the continuous supply of GTP fuel that the microtubule may persist.

The simplified dynamics of microtubule assembly.[1]

Organic chemists aim to mimic this lifelike property in minimal, chemical systems so that we can take advantage of their emergent properties: molecular motors, chemical oscillators and dissipative supramolecular materials all exist in non-equilibrium states and can perform work like their biological equivalents. However, whilst a process of minimal self-replication out-of-equilibrium may have far-reaching consequences for our understanding of minimal life, and inspire new functional systems, this area is underexplored.[2] We’re excited to report in Nature Communications (https://doi.org/10.1038/s41467-019-08885-9)[3] a system consisting of a self-assembled replicator which persists in an out-of-equilibrium state by the consumption of a chemical fuel.

A chemically fuelled self-replicator.[3]

In this system, a surfactant molecule is constructed in a biphasic reaction between components and 2. Above the critical micelle concentration this surfactant self-assembles into micelles, which catalyse the biphasic reaction required to form new surfactant 4. We therefore call them self-replicating.

However, the surfactant reported in this work is subject to an important destruction step;[4] the equilibrium position of the entire system is for the complete destruction of the replicator to thermodynamic products and 5, represented by the solid black arrows in the image above. The breakthrough came with the realisation that the low-energy, thermodynamic product could be used to regenerate the starting materials via a simple oxidation reaction. We could kick this system into an out-of-equilibrium state by the continuous consumption of oxidising chemical fuel (shown by the dashed grey arrows). The fuel allows the cycle to continue around in the direction of irreversible reactions, much like a simple metabolic cycle, maintaining the population of the surfactant in time. In hindsight the design was beautifully simple, but not intuitive!

The full behaviour of this system, responsive to variation in the supply of fuel, can be found in the full article (https://doi.org/10.1038/s41467-019-08885-9).[3] This system is neat, clean, and represents an advance even over many non-replicating systems by operating under the continuous supply of a chemical fuel.

The nature of the functional, out-of-equilibrium species as a supramolecular micelle presents many avenues for future exploration. For example, micelles can act as the compartments for other chemical reactions; if we can couple out-of-equilibrium micelle formation with another reaction then, in theory, we can control the behaviour of this second reaction in time.

These secondary reactions might offer an advantage to the micelles in which they occur and alter their stability under out-of-equilibrium conditions. We can also start to explore competing species and the persistence of different replicators under an out-of-equilibrium regime, competing for the starting material. Exploring these ideas will give rise to systems of increasing complexity, function and behaviour and we are keen to push the system to its limits.

1. Ragazzon, G. & Prins, L. J. Energy consumption in chemical fuel-driven self-assembly. Nat. Nanotechnol. 13, 882–889 (2018).

2. Ashkenasy, G., Hermans, T. M., Otto, S. & Taylor, A. F. Systems chemistry. Chem. Soc. Rev. 46, 2543–2554 (2017).

3. Morrow, S. M., Colomer, I. & Fletcher, S. P. A chemically fuelled self-replicator. Nat. Commun. 10, 1011 (2019).

4. Colomer, I., Morrow, S. M. & Fletcher, S. P. A transient self-assembling self-replicator. Nat. Commun. 9, 2239 (2018).

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Sarah Morrow

PhD student, University of Oxford

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