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Article
Subject Categories: Cell & Tissue Architecture | Structural Biology
The EMBO Journal (2006) 25, 302–311, doi:10.1038/sj.emboj.7600960
Published online 12 January 2006
Dynamic study of the transition from hyaluronan- to integrin-mediated adhesion in chondrocytes
Miriam Cohen1, 2, Zvi Kam1, Lia Addadi2 and Benjamin Geiger1
1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
2 Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel

To whom correspondence should be addressed
Benjamin Geiger, Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Tel.: +972 8 934 3910 or 4069; Fax: +972 8 946 5607; E-mail: benny.geiger@weizmann.ac.il

Received 22 August 2005; Accepted 6 December 2005; Published online 12 January 2006.
Abstract
Membrane-bound hyaluronan mediates the initial adhesive interactions between many cell types and external surfaces. In RCJ-P chondrocytes, such early contacts are mediated through a thick hyaluronidase-sensitive coat. The early adhesion is followed by integrin-mediated interactions and the formation of stable focal adhesions. During this process, the distance between the cell membrane and the surface is reduced from micrometers to few tens of nanometers. The transition from hyaluronan- to integrin-mediated adhesion was studied on glass surfaces by total internal reflection fluorescence microscopy. Hyaluronan-mediated adhesion precedes focal adhesions formation by 2–10 min. After these initial interactions, the pericellular hyaluronan remains sequestered into discrete pockets between the cell and the surface, which are a few hundreds nanometers thick and a few micrometers wide, and are flanked by focal adhesions. The hyaluronan coat facilitates the nucleation of small paxillin-rich contacts, which later mature into focal adhesions. These dynamic studies demonstrate that pericellular hyaluronan mediates initial cell–surface adhesion, and regulates the formation of focal adhesions.
Keywords: cell adhesion, hyaluronan, integrins, quantum dots, TIRF
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