Details of Grant 

EPSRC Reference:	EP/D501512/1
Title:	The development of a hybrid AFM instrument to elucidate the relationship between the biomechanical properties of cells & their interactions
Principal Investigator:	Wright, Dr C
Other Investigators:	Williams, Professor R Conlan, Professor RS
Researcher Co-Investigators:
Project Partners:
Department:	College of Engineering
Organisation:	Swansea University
Scheme:	Standard Research (Pre-FEC)
Starts:	01 October 2005	Ends:	31 March 2009	Value (£):	169,349
EPSRC Research Topic Classifications:	Instrumentation Eng. & Dev.
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:
Summary on Grant Application Form
How biological cells attach to surfaces and to one another is an important phenomenon that governs the outcomes of many processes in the natural world and industrial environments. Thus, the study of cell attachment has become the focus of a large amount of research with the ultimate aim to comprehensively understand these processes. With such understanding engineers and scientist can predict the behaviour of cells in processes as diverse as embryonic implantation and cell flocculation in brewery fermentations, and devise control regimes to prevent malfunction through disease in the case of medicine or technological advancement in industry for improved economic management.In order to comprehensively understand how cells attach to surfaces the scientist must be able to measure the forces that control the attachment process and the biomechanical properties of the cell. We are proposing to combine atomic force microscopy (AFM) with laser scanning confocal microscopy (LSCM) and high speed microscope photography (HSMP) to construct a unique instrument that for the first time will allow rigorous microscopic examination of the structure of a cell while it is brought into contact and retracted away from a surface under a controlled series of forces. This will permit the measurement of parameters, including the biomechanical properties of cells and adhesive forces, that are essential for the mathematical modeling of cell interactions with surfaces. AFM will function as a force sensor, raising and lowering the cell to a surface. In AFM force measurement a probe is located at the apex of a micronscale lever and the deflection of the lever is measured as the probe is brought into contact and retracted from the surface, the deflection can then be converted to a measure of force as a function of surface separation. Recent advances in AFM have allowed the scientist to pick up individual cells and bring them into contact with a surface with a controlled amount of force. In the combined instrument the cell will be brought into contact with a surface while monitoring the interaction from the side with HSMP and from below with LSCM. The HSMP will monitor changes in geometry as the cell deforms under the controlled force application from the bent lever. The LSCM will also monitor changes in geometry at a slower rate; however this technology allows 3 D imaging of the change in geometry. In addition, the LSCM can also monitor the distribution of macromolecules involved in specific interactions and the mechanical response of the cell when they are correctly labelled with fluorescent markers. This then allows the exciting possibility of correlating events observed with the HSMP and LSCM to phenomena quantified during the AFM force measurement. In cell-cell interactions the ability to view the interaction of the two cells will allow optimal alignment of the cells so that results are consistent.Once the combined instrument has been developed we will then use it to unravel the influence of the biomechanical properties of cells on their interaction with surfaces and other cells. To do this we have chosen three model systems that are important to medicine, process engineering and the natural environment those of yeast fibroblasts (mammalian)and Arabidpsis sp. (plant). We will commence work with yeast cell size mutants that are large enough to quantify changes in shape under examination from the HSMP and LSCM. We also have a range of yeast cell mutants that we can control the expression of molecules involved in adhesion and biomechanical response. To aid study we will change important environmental factors that control cell attachment and cell-cell interactions, these include pH, surface roughness and environmental additives such as antibiotics.
Key Findings
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Organisation Website:	http://www.swan.ac.uk