Matrix metalloproteinase activity synergizes with α2β1 integrins to enhance collagen remodeling

Cell-matrix interactions transmit a wealth of information about the extracellular environment. In return, a variety of responses from the cell are initiated by changes in the matrix. One such response involves the positive regulation of matrix metalloproteinases (MMPs) by α2β1 integrin attaching to a specific extracellular matrix component, collagen. This study explores the relationship between mechanical and biochemical functions of α2β1 integrins as it pertains to regulating matrix remodeling. To understand this relationship, the individual influences of MMP activity and α2β1 integrin function on collagen gel contraction were studied. We have observed little evidence of mutual participation in matrix remodeling by the α2β1 integrin and MMP activity in cell models where α2 is minimally expressed. In cells expressing high levels of α2, we see an increase in gel contraction that is enhanced by MMP activity. Measuring tension as it builds within the gel reveals that α2β1 integrin presence correlates with force output but is insensitive to MMP activity. These data strongly suggest that α2β1 regulates collagen gel remodeling through multiple simultaneous mechanisms including force generation and modulation of MMP activity.