Forum 04/23/2009

“The Molecular Architecture of Integrin-Mediated Focal Adhesion Revealed by Cryo-Electron Tomography”

Ohad Medalia, Ph. D. – Department of Life Sciences and The NIBN,  The Ben-Gurion University Beer-Sheva, Israel

Cell adhesions play an important role in the organization, growth, maturation, and function of living cells. Interaction of cells with the extracellular matrix (ECM) is curtail for a variety of disease states including tumour formation and metastasis, inflammation and repair of wounded tissues At the cellular level, many of the biological responses to external stimuli originate at adhesion loci, such as focal adhesions (FAs), which link cells, to the ECM or to their neighbors. Cell adhesion is mediated by receptor proteins such as cadherins and integrins. The accurate molecular composition, dynamics and signaling activity of these adhesion assemblies determine the specificity of adhesion-induced signals and their effects on the cell. However, characterization of the molecular architecture of FA is highly challenging, due to its complexity and technical aspects. I will show the 3D analysis of integrin-mediated cell adhesion using cryo-electron tomography of intact mammalian cells.  By means of correlating fluorescent and cryo-electron microscopy, we identified FAs and acquired 25 tomograms that were analyzed in 3D.