Mechanically Interfacing with Biology via Piezoelectric Nanowires

Collectively, cells can perform incredibly complex tasks. Their function allows us to interact with the world, fight disease and repair the materials that make us. The ability to control this behaviour could lead to significant advances in areas such as regenerative medicine, tissue engineering and bio-mimetic materials. However, interfacing directly with cells to dictate their behaviour is far from trivial. The chemical pathways and mechanisms that typically regulate cell function have been devised over millions of years of evolution, resulting in fiercely complex and finely balanced systems. Interfering with these schemes rarely succeeds. Interestingly, a new and emerging field of research known as mechanobiology may offer a solution to this problem. This describes the phenomenon whereby cellular systems are exceptionally sensitive to their mechanical environment, i.e., the function and behaviour of cells can be regulated by the physical properties of their surroundings and the forces that they experience. As an example, human stem cells grown on a soft substrate are likely to differentiate into fat cells, while growing those same stem cells on a rigid substrate will lead to the formation of bone cells. The challenge of controlling cell function is then shifted to the challenge of controlling the mechanical properties of cell surroundings. In this context, piezoelectric materials are ideal candidates for tools within mechanobiology, given their ability to both detect and apply small forces. By combining piezoelectric materials with a grid of electrodes, similar to that found on the touch screen of a phone, a 'touch screen for cells' can be created. Cells growing on this device will exert a force on the piezoelectric material, causing it to develop some electric charge. This charge can then be detected with some degree of spatial resolution using the grid of electrodes. Furthermore, via the same grid of electrodes, individual areas of the piezoelectric interface material can be excited to provide local mechanical stimulation to a specific part of the platform. In this way, an effective bio-electromechanical interface can be created to both electrically detect and apply physiologically relevant mechanical forces on cells to manipulate their functionality.

Meeting the materials selection criteria for the piezoelectric element is challenging, as what is required is a small, flexible and biocompatible piezoelectric structure to interact with cells. Nanostructured piezoelectric polymeric materials are ideally suited for this purpose as cells are themselves typically micron sized and exert forces in the pico- to nanonewton range. The proposal therefore aims to develop appropriate biocompatible piezoelectric polymer nanowires as the bio-electromechanical interface material, thus leading to the development of a powerful tool for synthetic biology. The proposal uniquely aims to undertake inter-disciplinary research involving the application of cutting-edge materials science and engineering to develop new and exciting tools for bioscience research.

It has become increasingly evident that the mechanical environment of a cell is crucial in determining its behaviour, and the subsequent long range morphology of multicellular systems. In this regard, functional and responsive nanomaterials can provide a convenient route towards achieving a bio-electromechanical interfacing platform with advanced functionality. With the platform outlined in this proposal, the possibility arises for directly sensing and actuating extracellular forces within a cellular environment for the first time under external and addressable dynamic electric field control. Piezoelectric materials make this possible due to their ability to inter-convert mechanical and electrical energy, and piezoelectric nanomaterials in particular are ideal candidates for tools within mechanobiology, given their ability to both detect and apply small forces on a length scale that is compatible with cellular dimensions. While the proposal targets a fundamental understanding of electromechanical properties of bio-compatible piezoelectric polymernanowires and their interactions with cells, the findings will be directly relevant to developing a simple and inexpensive technology that would allow for a high throughput of synthetic biology experiments with minimal unwanted influence on the cell behaviour.

In order to achieve spatial resolution to the electrical signals being applied to or detected from the bio-electromechanical interface, an array of electrode 'pixels' is required to address sections of the piezoelectric nanowire array via a pre-patterned and electroded substrate. The resulting piezoelectric bio-electromechanical interfacing tool will be tested across a variety of cell lines. The proposal thus aims to rise beyond the limitations of the available methods to apply physiologically relevant stress profiles on cells, particularly with sub-cellular resolution, through external electric field manipulation, with simultaneous force sensing capabilities.

This project is aiming at providing significant breakthroughs in terms of developing a novel bio-electromechanical interfacing technology with wide-ranging applications in healthcare, regenerative medicine, bio-mimectics and synthetic biology, to name a few. The long term societal and economic impact of this project can be significant in particular through these diverse applications. For example, the ongoing revolution in synthetic biology, underpins a growing multi-billion £ global market with a rich activity in the UK. Advances in cell-imaging and cell-interfacing can potentially revolutionise the healthcare market, including delivering personalised healthcare, rapid and non-invasive diagnostics, and offering an active platform to better understand physiology in health and disease. Perhaps the most exciting possibility of such an advance would be dynamic remodelling of tissues in a manner analogous to bone remodelling. External and addressable control over intercellular mechanical signals could have numerous medical or industrial applications for generating advanced composite materials in arbitrary shapes using low intensity energy sources, and would represent an entirely new route to fabrication of bulk materials. The proposed bio-electromechanical interface thus presents significant potential for both innovation and exploitation. This will drive innovative and sustainable bio-medical tools in the UK for 21st century products, delivering a step change in both throughput and breadth of application to facilitate new research discoveries.

Key technology outcomes from this project will be identified and translated to commercial exploitation quickly and efficiently, through collaboration, patenting/licensing and entrepreneurship. Cambridge Enterprise, which is the technology transfer division of the University of Cambridge, will oversee IP and commercialisation arrangements. It is envisaged that the piezoelectric nanowire bio-platform will create ideas which can attract funding from other sources to further support exploitable concepts and provide fertile ground for the generation of spin-off companies. Cambridge provides unique access to its vibrant science parks including the Cambridge Biomedical Campus, and thus fertile ground for exploitation of new concepts to achieve commercial success. The EPSRC and BBSRC also provide a funded route for UK researchers to access a wider academic-industrial network via the SynbiCITE, which is also accessible to the UK and global industry. Hence the developed knowledge and processes will be directly available to all stake holders via this network, and represents an immediate route to impact. As well as transferring knowledge and expertise into industry, the broader public and policymakers will be educated about this research and its potential impact. The PI has a strong track record in public engagement and outreach to young people and the general public and will continue to inspire the public at an influential level on technology related societal challenges and opportunities.