Chemically diverse polyacrylate and acrylamide surfaces for human cardiomyocyte culture and their effect on phenotype
PhD Supervisor(s): Chris Denning, Morgan Alexander, Martyn Davies.
Contact Email: mzxap1@nottingham.ac.uk
Undergraduate Degree: Master of Pharmacy (King’s College, University of London)
PhD Summary
Cardiomyocytes derived from human pluripotent stem cells have been shown to respond appropriately to pharmacological agents, model disease and have the potential to be used in clinical applications. However, they remain functionally immature. To allow for wide scale use of these cells, there is a need to improve culture conditions. Firstly, to provide more economical, defined and reproducible surfaces for culture and secondly to assess if surface chemistry can effect maturity of cardiomyocytes.
My research focuses on identifying synthetic surfaces suitable for human cardiomyocyte culture using a high-throughput approach. Microarray technology developed by our collaborators at Massachusetts Institute of Technology (MIT) was employed to identify substrates that allowed attachment and proper myofibril alignment of the cardiomyocytes. Suitable surfaces were then taken forward to perform more detailed cardiomyocyte characterisation including electrophysiology, protein and gene expression with a particular focus on those that give an indication of maturity. Furthermore, correlation of surface properties with cell attachment was attempted using a multivariate regression technique, Partial Least Squares, which identified potential chemical moieties important for attachment.
The multi-disciplinary nature of this project means that I have had the opportunity to become skilled at acquiring surface characterisation data using time of flight mass spectrometry and water contact angle measurements and analysis of data from x-ray photoelectron spectrometry. As well as becoming competent in human stem cell culture, differentiation and cell characterisation techniques such as immunochemistry, polymerase chain reaction and electrophysiology using patch clamping.
The high-throughput nature of the project has also required the development of cell analysis software protocols to exploit the volume of data acquired using automated microscopy.
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