CONTROL OF CELL-CYCLE PROGRESSION BY FIBRONECTIN MATRIX ARCHITECTURE

Developmental patterning and differentiation, maintenance of parenchym al cell function, and the size, shape, and invasiveness of tumors are all orchestrated by cell interactions with the extracellular matrix. H ere we show that the fibrillar structure of fibronectin (FN) matrix en codes essential regulatory cues and controls cell proliferation and si gnaling through changes in matrix architecture. A matrix assembled fro m native FN stimulated cell growth. In contrast, a mutant FN (FN Delta III1-7) that contains all known cell binding motifs but forms a struc turally distinct matrix inhibited progression from G(0)/G(1) into S ph ase. Furthermore, FN Delta III1-7 suppressed the stimulatory capacity of native FN and induced different levels of tyrosine phosphorylation of pp125(FAK). The differential effects on cell growth were ablated by blocking formation of matrix fibrils. Thus, modification of matrix ar chitecture provides a novel approach to control cell proliferation.