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Matrix degradation
The extracellular matrix (ECM) is a complex meshwork of proteins and proteoglycans that provides structure and support for cells and tissues. A simplified diagram of the 
composition of the extracellular matrix is on the right. Collagen is one of the major constituents of the ECM existing in many different types depending on the tissue and often forming fibres. Fibronectin and laminin are two other protein constituents of the ECM, while the bulk of the space is usually taken up by very large proteoglycan molecules.
In vitro studies of cell migration are often performed on 2-dimensional surfaces such as plastic and most cells are able to move freely on these surfaces (see movie below left). By contrast cells embedded in a 3-dimensional matrix such as collagen are constrained in their movement (see movie below right).
Cells migrating on a plastic surface |
Cells embedded in a collagen matrix |
In order for cells to move through the extracellular matrix an additional step in the migration process is required - the degradation of the matrix in order to create space through which the cell can move. This can be 
achieved by the secretion of proteases such as the matrix metalloproteinases (MMPs).
The image on the right shows collagen fibres in the matrix that was used to embed the cells shown in the movie above right. The dense fibre network makes it difficult for the cells to move. Secretion or surface expression of MMPs by the cells allows degradation of the ECM and promoting cell migration. There are a number of different MMPs, each with slightly different targets in the ECM. For example, MMP1 targets collagen and MMP9 targets gelatin. The activity of MMPs can be regulated by nitric oxide (nitrosylation of MMP9, for example, is known to increase its activity) and by a class of enzymes called TIMPs - or Tissue Inhibitor of Matrix metalloproteinases - which inhibit MMP activity.
Degradation of the extracellular matrix is often accomplished through specialised structures known as podosomes or invadopodia. These are protrusions of the plasma membrane that extend into the extracellular matrix and from the ends of which MMPs are secreted. A simplified diagram of an invadopodium is shown below.
