Fibroblast growth factors, nanoparticles and photothermal imaging: 1st delivery

Laurence’s paper on the transport of FGF-2 in the pericellular matrix (or glycocalyx) of fibroblasts is now published in PLoS Biology. There is a nice summary too. The paper demonstrates two new and very important properties of matrices.
Firstly, that movement of effectors such as FGF-2 only needs cycles of binding and dissociation from heparan sulfate. This is all that is necessary for an effector to get from its source cell to its target cell. Since most soluble protein effectors are like FGF-2 and bind heparan sulfate in matrix, this will be a general phenomenon. Secondly, that the binding sites for FGF-2 are not randomly distributed, but instead are organised over very long distances (micro metres).
The gestation of this paper has been rather long. It started in 2001 in the course of a discussion between myself and three colleagues in the Department of Chemistry, David Schiffrin, Richard Nichols and Mathias Brust. It was a simple recipe: nanoparticles, add a protein, image and get an instant readout of stoichiometry, dynamics, etc., etc. The funding bodies and referees thought so too. So why 10 years? Did we fall asleep?
Not quite. Ligand shells for nanoparticles were not up to scratch, so we spent 75% of the first tranche of grant funding solving a problem that, according to the literature was already solved. It wasn’t until 2008 that we devised a really good ligand shell for gold nanoparticles, which would allow highly specific interactions with target molecules. We were planning to use scattering for imaging, but that was never going to work with small gold nanoparticles. Enter, stage left, Brahim Lounis in Bordeaux and his photothermal microscope with the ability to track single nanoparticles at video frame rates with 13 nm pointing accuracy. This collaboration led to the Liverpool Centre for Cell Imaging engaging in its first exercise of home build, led by Raphel Levy: we now have two photothermal microscopes dedicated to live cell imaging. Wouldn’t it be nice to get an ultrastructural picture? Ian Prior and his Biomedical Electron Microscopy Unit to the rescue, with membrane rips. How are we going to analyse this mountain of data and what does it mean? Rachel Bearon from Maths with some great Matlab scripts.
Now onto the next one – we are much, much faster and only a year away!

Read Full Post »

Leica Scientific Forum

Dr. Kees Jalink, Netherlands Cancer Institute (NKI-AVL), Amsterdam, NL will be giving a seminar entitled

“Zooming in on signal transduction by FRET – How to optimize a FRET sensor… and how to use it” on

Tuesday 10th July at 5pm

Lecture Theatre 1, Sherrington Building, with a post lecture reception at 6.15pm in the foyer outside the lecture theatre.

This is particularly relevant to those interested in signaling and measuring how the interactions of molecules impacts on signallling.  More details on Dr. Kees Jalink’s website.

Read Full Post »