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Details of Grant 

EPSRC Reference: EP/Y002245/1
Title: Probing the mechano-biology of cell-cell adhesion in a novel single cell assay
Principal Investigator: Koester, Dr DV
Other Investigators:
Researcher Co-Investigators:
Project Partners:
IISER Kolkata PRECISE Center, University of Pennsylvan Raman Research Institute
Department: Warwick Medical School
Organisation: University of Warwick
Scheme: Standard Research - NR1
Starts: 01 March 2024 Ends: 28 February 2026 Value (£): 165,354
EPSRC Research Topic Classifications:
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
24 May 2023 ECR International Collaboration Grants Panel 3 Announced
Summary on Grant Application Form
We, animals and many other organisms are built from lots of cells. These are not simple building blocks that are passively stuck together, but each cell contains an elaborate machinery to connect to its neighbours and exert force on one other. This crucial ability is provided by multiple adhesion molecules at the cell surface that link up to the force generating cytoskeleton via adapter proteins. The balancing of forces and how strong different cells stick to each other are all important cues in the orchestration of cell motion and differentiation during development. And it is now clear that mechanical changes on the cellular level can alter the fate of the tissue. In cancer, the detachment of cells leading to metastasis is related to a change of cell mechanics.

We are interested to dissect the basis of intracellular mechanical signalling in cell-cell adhesion. For this, we are establishing a new international collaboration to study the role of forces in the process of cell adhesion. We use novel assay to look at the cell-cell adhesion interface with high resolution fluorescence microscopy by replacing one cell with a planar lipid bilayer containing adhesion molecules. This will be combined with three modes of mechanical manipulations: confinement, shear stress and lateral stretch. In addition to fluorescence microscopy techniques to follow the dynamics of adhesion and cytoskeletal proteins, we will employ interferometric reflection microscopy to reveal the fluctuations of the cell membrane with nanometre precision. This will give us an unprecedented insight into the protein dynamics and cell membrane mechanics during cell adhesion.

The tools for such experiments are often built by individual labs which limits the range of people having access to such equipment. That's why we want to use the combined expertise of this collaboration to design and engineer MechanoWOSM, an open source microscope platform for mechano-biology experiments.

Key Findings
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Date Materialised
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Organisation Website: http://www.warwick.ac.uk