A new instrument will trap individual human cells in laser beams, snip tiny patches from their outer membranes, and chemically analyse the molecules found there. The project addresses a fundamental gap in biology: scientists know the genetic code for making proteins, but they cannot easily measure which proteins and lipids are actually present in a specific part of a single cell’s membrane. These molecules determine how a cell communicates, moves, and responds to its environment. Current techniques average signals from thousands of cells, hiding the differences between individual cells that drive health and disease. If successful, the instrument will combine microfluidics, optical trapping, and 2D infrared spectroscopy to digest and identify molecules from a single cell’s plasma membrane. This is primarily fundamental science—it aims to reveal the molecular machinery of cell surfaces at an unprecedented scale. In the long term, such understanding could underpin new approaches to drug delivery, cancer diagnostics, or tissue engineering, where knowing exactly which molecules sit on a cell’s surface determines how it interacts with therapies or other cells.
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The human genome project and those aimed as sequencing the genomes of other organisms tell us the codes that are present in an organism for generating proteins. Of course nearly every cell in the body contains a complete copy of those codes yet there are numerous cell types within the body performing a wide range of different functions, even within the same tissue we can clearly identify different cell types that are performing widely different functions. What makes these cell types different is fundamentally the different level of expression of the genes that they contain, in other words the genes that are switched on and therefore the proteins that are manufactured within those cells. However that is not the whole story. Even if we know what genes are switched on in a cell, the down stream activity of those proteins is really what is important in determining cell functionality. Proteins will move within the cell, they will interact and transform depending on those interactions. In addition the cells contain a wide variety of other chemical species, not least of which are lipids. While not directly coded by the genome, the production of lipids within the cell is controlled by the proteins present and interactions involving lipids are equally important in cell function as those involving proteins.One important area where understanding of the mechanisms behind cell function is at the cell membrane, as it is here that the cell interacts with its environment and with other cells. The ability to determine which molecular species are present within the cell membrane, particularly in areas where we can identify some sort of activity will be key to developing this understanding. This proposal is an ambitious project to construct instrumentation that can take individual cells, extract those molecules from identified areas of the plasma membrane, and analyse them using optical techniques to determine the chemical structures that they contain. The proposed instrumentation draws together a number of individual technologies from across Imperial College: The whole process will take place in microfluidic devices where fluids can be handled in nano-litre volumes to digest and separate molecules from cells and from each other: Multi-dimensional fluorescence imaging techniques will be used to highlight the interesting and active areas on the cell membrane and to monitor the digestion process: Optical trapping will be used to hold and manipulate the individual cells within the microfluidic flow to allow targeting of specific areas of the cell membrane: 2d non-linear infra-red spectroscopy techniques will be used to analyse the digested components and determine their structure.
Andrew De Mello (Co-Investigator)David Klug (Principal Investigator)Keith Willison (Co-Investigator)Mark Neil (Co-Investigator)Paul Michael William French (Co-Investigator)Peter Parker (Co-Investigator)Richard Templer (Co-Investigator)
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