(500g) Contact Guidance Differs On Micropatterned Collagen Substrates and Organized Collagen Fibers

Before metastasis occurs, collagen fibers are reorganized around the tumor by surrounding stromal cells. The fibers transition from a circumferential pattern with collagen fiber alignment parallel to the tumor margin to a radial pattern with collagen fiber alignment perpendicular to the tumor. This change in organization directs cells to migrate along the radially organized collagen fiber bundles to surrounding tissue in a process called contact guidance. While qualitative knowledge of contact guidance is well-established, quantitative details associated with how local collagen organization promotes directed migration during contact guidance is lacking. We have been using two approaches to induce directed migration on 2D surfaces. In the first approach collagen is patterned on glass using microcontact printing. This approach results in potent directional cues that can be moderately tuned based on line spacing and background adhesion strength. In the second approach collagen fibers are grown on atomically smooth mica surfaces. By tuning buffer conditions, fibers of different sizes and fields of fibers with different degrees of alignment can be generated. This approach results in two interesting behaviors. First, large diameter collagen fibers induce random migration even when aligned, whereas small diameter collagen fibers induce potent directed cell migration. Second, the random migration on large fibers appears to be distinct from random migration on glass. These large organized collagen fibers appear to stimulate migrational behavior similar to that seen in 3D environments, where cells make many directional changes by extending protrusions that split and retract. Consequently, while microcontact printed surfaces generate a fairly potent approach for directing migration, assembled collagen fibers that organize into aligned patterns on mica surfaces constitute a better mimic of 3D environments and stimulate rich behavior that is highly sensitive to the underlying collagen organization.