Direct observation and characterisation of physical autocatalysis by interferometric scattering microscopy

Autocatalytic chemical reactions have been extensively studied with the aim of providing insight into the principles underlying living systems. In biology, organisms can be thought of as imperfect self-replicators, which produce closely related species, allowing for selection and evolution. Autocatalysis is also an important part of many other biological processes.

This project aims to develop new autocatalytic reactions where two simple chemical building blocks come together to give a more complex product, and then the product aggregates to give primitive cell-like structures or "protocells" such as micelles or vesicles. The protocells allow the starting materials to mix more efficiently, speeding up the reaction in time and giving rise to complex behaviour of the protocells. A new ultra sensitive microscope will be used to monitor the formation and dynamics of the protocells in real time. These reactions will serve as model systems which we hope will contribute to understanding how complex cell-like systems can emerge from much simpler chemical components and may be relevant to understanding the principles of how life started on earth.

The potential economic and societal benefits of this work will likely arise from an increase in understanding of how some complex systems work, the new technologies that are available for ultra-high resolution imaging, and the development of new model systems for living cells.

Life is the most prominent example of a far from equilibrium state, and elucidating the nature of the subtle organizing principles upon which such systems operate is an enormous challenge. The overall objective of the work is to understand complex phenomena related to complex emergent systems where we aim to design and study new systems and then to use the lessons learned in this process to establish rules for how these systems work, to see if we can observe novel phenomena, to understand what factors control these systems, and to see if these systems can be tuned rationally. This work aims to deliver a real advance in the rational design of complex cell-like materials from simple chemical building blocks and is likely to open up completely new avenues of research. Understanding how complex collective behavior can spontaneously emerge is (as mentioned in other sections of this application) relevant to two EPSRC and one U.S. Department of Energy, Grand Challenges. While the impact of understanding the appearance of states far from equilibrium may not be felt for sometime, this area of research is likely to enable new arenas of experimentation, control and modelling.

More immediate beneficiaries of this research may arise from the unique imaging capabilities of iSCAT. We are exploring in which ways the capabilities of iSCAT outperform the current state-of-the-art in label-free biosensing. Surface plasmon methods are a well-developed and important technology with numerous industrial applications. iSCAT not only promises orders of magnitude higher sensitivities down to the ultimate single molecule limit, but also three orders of magnitude faster response times (10 kHz) compared to state-of-the-art SPR sensing (10 Hz), which would enable studies of a completely new variety of protein-protein interactions. The work proposed here will be instrumental in not only demonstrating the sensitivity of the technique, but also its versatility. In this context, we aim to use the results obtained here to approach major players in the surfactant industry where iSCAT could provide completely new insight into the dynamics of nanoscale objects in solution.

This research could lead to advanced materials in the form of cell-like systems that are capable of performing a function. The 'protocells' developed here exhibit complex dynamics and understanding and controlling this behaviour holds tremendous potential in terms of synthetic biology and developing model systems. Chemical models of cells that can mimic living systems will serve as useful models in mathematics, physics, chemistry, biology, nano-technology and medicine. In the long term, the development of such devices could potentially bring benefits to high-tech manufacturing, as well as medical researchers, clinical scientists and ultimately their patients. The long term benefits from understanding how construct and control dynamic systems similar to living cells are potentially huge to the economy of the UK. "Synthetic Biology for Growth" is a programme supported by the RCUK and has been identified as one of the "Eight Great British Technologies of the Future". Understanding how to design life-like systems could have tremendous implications in terms of quality of life and health.