Protolife-inspired materials chemistry

Making new materials that have small-scale structures and multiple components is expected to be of great importance in a wide range of applications such as sensing, storage and release operations, and controlled catalysis. One new area where small-scale structures could make a significant breakthrough is in the formation of artificial cell-like materials (protocells). Much of the inspiration for this approach comes from mimicking key aspects of the living cell, albeit with a large degree of simplification. Our approach to addressing the necessary simplification is to draw inspiration from imaginative scenarios that are being considered as plausible mechanisms for prebiotic organization on the early Earth. We are therefore inspired by these protolife-based models of materials organization to develop new strategies in the laboratory that will result in the design and construction of chemical micro-compartments with novel properties and functions. In a sense, we aim to abstract ideas about the past in order to develop new technologies for the future.

Our work will advance new technologies for the preparation of novel types of organized microscale architectures that are spontaneously assembled from multiple components, and which when combined together exhibit special functions. The proposed work has three main themes that will help us develop guidelines for the rational design and construction of new classes of integrated materials based on artificial cell-like micro-compartments using biological and non-biological components. The themes are focused on the synthesis, properties and utilization of self-assembled protocells involving (a) protein-polymer building blocks, (b) inorganic nanoparticle membranes, and (c) membrane-free micro-droplets. In each case, we intend to discover new methods of chemical construction, including the building of supramolecular structures within and on the micro-compartments to produce soft hydrogels that are similar to the cytoskeletal matrix, building of external coronal layers to control the diffusion of ions and molecules through the membranes, and incorporation of diverse components inside the protocells for controlled reactivity. For example, we intend to prepare protocells with encapsulated nanoparticles that can be exploited in photo-activated processes such as the splitting of water molecules. By confining these processes within small-scale architectures, we expect to achieve new levels of control and activity, which will provide new breakthroughs in the emerging area of bioinspired materials chemistry.

Academic benefits (See Academic Beneficiaries).

Technological impact:
By developing a portfolio of three different protocell models, the proposed work will not only generate transformative ideas in materials chemistry at the interface with biology, but will also spearhead long-term advances in Living Technologies focused on the ex novo synthesis of minimal life constructs. For example, uses in remote operations sensing in biological and non-biological milieu, monitoring and delivery of therapeutic agents in medicine, development of microscale and nanoscale motors and actuators, and decontamination of water-based environments can be envisaged. Protolife-inspired research will also be of significant interest to industrial partners in fields such as energy storage, carbon fixation, water splitting, health and personal care, and advanced composite micro-engineering.

Economic benefits:
The ability to address new technological futures by abstracting problems implicit to the deep past is a promising and significant source of new ideas for wealth creation. In this regard, the proposed work opens up novel possibilities for new disruptive technologies based on soft, wet, chemical microsystems with adaptive and self-referential properties. Specifically, protolife-inspired technologies will be useful in areas such as microscale chemical organization, functional materials micro-ensembles and bioinspired constructs. The proposed research therefore offers benefits in diverse markets such as those currently dominated by companies such as Unilever and GSK, who require continual innovation in microscale compartmentalized materials for new delivery, storage and release systems.

In terms of the specific research programmes, protocells with controlled membrane permeability could have important implications in micro-reactor technologies and applications involving the storage of biomolecules in liquid media, recursive uptake of substrates and cofactors for compartmentalized reactions, and sustained self-controlled release of drug and bioactive agents. In addition, studies on photoactive protocells offer a novel route to the fabrication of nanoparticle-mediated catalytic micro-reactors with potential benefits for bio-remediation, and more speculatively, in microscale energy conversion (water splitting etc). Thus, our work should have a significant impact on promoting new activities that could increase the competitiveness and economic performance of UK-based sectors involved with applied soft matter and particle technologies.

Societal benefits:
The fabrication of synthetic protocells could have significant long-term impact on health care and quality of life. For example, artificial cells that are designed for specific applications in which the properties of biological systems (self-organization, nano-component efficiency, adaptability etc) are compartmentalized at a relatively low cost could give rise to new miniaturized agents for applications in DNA sequencing, molecular screening, soft matter biotechnology, energy conversion in microscale bio-batteries, pharmacology and medical diagnostics. Such areas can be viewed in the context and application of synthetic biology, and should aid downstream industrialization. In terms of a specific example, our recent published work on the coacervate-mediated enhancement in the yield of polyketide shunt products, suggests that adopting this approach for the laboratory manufacture of complex bioactive molecules could be widely beneficial. Significantly, in contradistinction to more radical forms of synthetic biology, the chemical construction of artificial cells provides an approach to life-like constructs with minimal evolutionary capacity, and as such would be more ethically acceptable in diverse biotechnological, environmental and medical applications.