Creativity@Home - Designer magnetic particle tagging and activation of mechano-sensitive receptors for remote control of cell signalling and behaviour

A recent major catalyst in aiding us to understand how cells respond to mechanical environment has been the advances in cell and tissue engineering and the regenerative medicine field. With the strong multidisciplinary framework for this field, we have been able to advance the potential for using tissue mechanics in defining how we grow and repair tissues. Alongside this we can ask basic questions about mechanotransduction which allows us to address major questions in this field. Seeking new therapies for regenerative medicine treatments has led to the utilisation of cells, in particular stem cells, for repair and replacement tissues. The use of living cells as a therapy presents several challenges; the most focal one being how to control therapeutic cells in the body. In our lab, we have established 2D and 3D tissue engineering models which allow us to develop therapies for regenerative medicine but also enable us to create more biological models for testing and understanding the role of mechanics in tissue biology and pathology. We have developed magnetic nanoparticle based strategies for tagging cell receptors and controlling cell behaviour and mechnotransduction. This project allows us to research into new multidisciplinary methods for specific magnetic particle tagging of cell mechano-sensitive receptors present internally and externally in a cell.

With ageing and disease, many musculoskeletal tissues lose the ability to regenerate and repair resulting in impaired function and severe pain. Disease of the musculoskeletal system is the most commonest cause for severe and long lasting pain and physical handicap in humans and effects millions worldwide. The number of bone fractures due to osteoporosis has doubled in the last decade and approx. 40% of women over 50 years of age will be affected. In children, diseases that deform and paralyze will continue to deprive children of their childhood. It is expected that 25% of health care costs in the next decade will be due to trauma related care with increasing demand for tissue regeneration efforts. A major drug development target by the pharmaceutical industry is osteoarthritis (OA), a degenerative disease of cartilage. OA affects nearly 21 million people in the US, accounting for 25% of visits to primary care physicians, and half of all NSAID prescriptions. It is estimated that 80% of the population will have radiographic evidence of osteoarthritis by age 65. Astra Zeneca has recently closed the OA division within the R&D UK headquarters. This is a clear sign that existing drugs do not have solutions. It is known that osteoarthritis can be correlated with mechanical function and we suggest that mechanoagonists may be potential targets for new forms of treatment. Finally more generically, in the search for new drugs, ion channels have become a favourite target since they provide the ability to regulate many physiological processes including pain, incontinence, diabetes, epilepsy, migraine, allergy and asthma, glaucoma, stroke, irregular heat beat and cancer. According to a recent market report, the 28 ion channel drugs currently on the market target just five ion channel proteins, but they still generate worldwide sales in excess of $12 billion (average revenue $400m per drug). Given that 406 ion channel genes have been identified, representing some 1.6% of the human genome, ion channels as a class of drug targets appear to be under exploited due in part to a failure to find suitable small molecule drugs. The ability to target the ion channels with mechano-agonists has yet to be exploited hence the impact of our programme has the potential to be of major relevance to this community.