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A more recent version of this article appeared on March 1, 2004
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Submitted on July 25, 2003
Revised on November 25, 2003
Accepted on December 2, 2003
5
1-mediated cell cohesion
1 UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903
2 Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903
* Corresponding author. E-mail address: corbetsi{at}umdnj.edu.
Integrin-extracellular matrix (ECM) interactions in two-dimensional (2D) culture systems are widely studied (Goldstein and DiMilla, 2002; Koo et al., 2002). Less understood is the role of the ECM in promoting intercellular cohesion in three-dimensional environments. We have demonstrated that the 
5
1 integrin mediates strong intercellular cohesion of 3D cellular aggregates (Robinson et al., 2003). To further investigate the mechanism of 51-mediated cohesivity, we used a series of chimeric 51-integrin expressing cells cultured as multilayer cellular aggregates. In these cell lines, the 5 subunit cytoplasmic domain distal to the GFFKR sequence was truncated, replaced with that of the integrin 4, the integrin 2, or maintained intact. Using these cells, 51 integrin-mediated cell aggregation, compaction and cohesion were determined and correlated with FN matrix assembly. The data presented demonstrate that cells cultured in the absence of external mechanical support can assemble a FN matrix that promotes integrin-mediated aggregate compaction and cohesion. Further, inhibition of FN matrix assembly blocks the intercellular associations required for compaction, resulting in cell dispersal. These results demonstrate that FN matrix assembly contributes significantly to tissue cohesion and represents an alternative mechanism for regulating tissue architecture.
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