Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
The Molecular Architecture of Integrin-Mediated Focal Adhesion by Cryo-Electron Tomography
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. Here we present the first 3D analysis of integrin-mediated cell adhesion using cryo-electron tomography of intact cells. By means of correlating fluorescent signal and electron microscopy, we identify FAs and acquired insight into their molecular architecture. This analysis revealed detailed information on the organization of filamentous actin, such as directionality, position and partial occupancy, at these loci. In addition, our data suggest that the cytoplasmic plaque of the adhesion machinery is composed of large number of macromolecular assemblies, spaced by a short distance.
Dept of Life Sciences and the NIBN