Paris, October 11, 2007
The eye's lens focuses light and forms a sharp image on the retina thanks to the organization and specific properties of its constituent cells (see box overleaf). As in all tissues, cellular exchanges are essential for nutrition and removal of waste products, but in the eye they must nonetheless be adapted to the particular properties of the lens. The membranes of lens cells contain protein assemblies, the aquaporins and connexons(2): the former act as water channels and the latter as channels for metabolites and ions. Together these membrane proteins ensure cell adhesion.
Using atomic force microscopy (AFM), which images the surface of a sample at a precision of one nanometer (one billionth of a meter), Simon Scheuring's team at the Institut Curie is studying how these protein assemblies function. An atomically sharp tip is scanned over the sample surface and its movements are tracked by a laser. The resulting data can be used to draw a topographical map of the sample. By comparing assemblies of aquaporins and connexons in membranes of healthy and diseased lens cells, Scheuring and colleagues have identified the biological changes that cause cataracts (see box overleaf).
In this senile cataract, lack of connexons prevents formation of the channels ensuring cell to cell communication. These molecular modifications explain the lack of adherence between cells, waste accumulation in cells, and the defective transport of water, ions, and metabolites in a lens with a cataract.
This is the first time that high-resolution AFM imaging of diseased tissue has shed light on the molecular cause of a disease at the single membrane protein level. A step towards medical nanoimaging has been taken with atomic force microscopy.
1) “Atomic force microscopy of proteins in native membranes” team in the Curie Physical Chemistry research unit UMR 168 CNRS/Institut Curie directed by Jean-François Joanny.
2) A connexon is an assembly of 6 connexin molecules and forms a gap junction between the cytoplasm of two adjacent cells.
3) The supramolecular architecture of junctional microdomains in native lens membranes
N. Buzhynskyy, R. Hite, T. Walz, S Scheuring. EMBO R. January 2007, vol. 8, p. 51-55.
Human cataract lens membrane at subnanometer resolution
Nikolay Buzhynskyy(1), Jean-François Girmens(2), Wolfgang Faigle(3) & Simon Scheuring(1)
1) Institut Curie, UMR168-CNRS, Paris.
2) Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Service IV & CIC, Paris
3) Institut Curie, Laboratoire de Spectrométrie de Masse, Paris
J. Mol. Biol. doi:10.1016/j.jmb.2007.09.022
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