Imaging cellular function on the nanoscale
Lead Research Organisation:
University of Cambridge
Department Name: Chemistry
Abstract
Livings cells are based on molecules and assemblies of molecules interacting with each other to form more complex structures and to enable the cell to respond to changes in its environment. To understand how living cells work we need to develop method to initiate these process in a controlled way so we can then follow what happens with a resolution that can visualise the key components.Since cells are soft and responsive one needs a way to do this which does not involve contact and we have developed a method of imaging the cell surface using a nanopipette which senses the cell surface by the reduction in current flowing through its tip. We have recently made a breakthrough in the way we image cells by moving the pipette like a sewing machine over the surface, which allows us to jump over large features which are very common on cells. We now want to exploit this advance to be able to also alter the cell in a controlled way, by either deforming the cell or delivering molecules that will initiate signals inside the cell, to be able to start to relate the cell structure to its function. We will develop a method to map and characterise some of the key structures and molecules on the cell surface. After firstly developing and refining these method on model samples we will then apply them to live cells to demonstrate that imaging function with very high spatial resolution is now possible.
Organisations
People |
ORCID iD |
David Klenerman (Principal Investigator) |
Publications
Babakinejad B
(2013)
Local delivery of molecules from a nanopipette for quantitative receptor mapping on live cells.
in Analytical chemistry
Clarke R
(2016)
Low Stress Ion Conductance Microscopy of Sub-Cellular Stiffness.
Clarke RW
(2016)
Low Stress Ion Conductance Microscopy of Sub-Cellular Stiffness.
in Soft matter
Clarke RW
(2013)
Pipette-surface interaction: current enhancement and intrinsic force.
in Journal of the American Chemical Society
Clarke RW
(2021)
Theory of cell membrane interaction with glass.
in Physical review. E
Jönsson P
(2012)
Hydrodynamic trapping of molecules in lipid bilayers.
in Proceedings of the National Academy of Sciences of the United States of America
Klenerman D
(2013)
Imaging the cell surface and its organization down to the level of single molecules.
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Zhukov A
(2012)
A hybrid scanning mode for fast scanning ion conductance microscopy (SICM) imaging.
in Ultramicroscopy
Description | We have developed a method to map the mechanical properties of the cell at the nanoscale and locally deliver reagents to defined positions on the cell. |
Exploitation Route | This method can be used to image the mechanical properties of cells and map mechanosensitive ion channels using scanning ion conductance microscopy. |
Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | This is a new method to probe the mechanical properties of cells on the nanoscale and excite mechanosensitive ion channels without contact and map their position |
First Year Of Impact | 2008 |
Sector | Healthcare |
Description | Responsive mode |
Amount | £367,000 (GBP) |
Funding ID | EP/L027631/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2018 |
Title | Mapping mechanical properties in the nanoscale |
Description | We have developed a method to map the cell surface on the nanoscale and measure the mechanical properties with a wide range of stiffnesses |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | We are in the process of writing this work up |