Fibroblasts and Cell Mechanobiology

This paper summarizes how fibroblasts respond to topography and cyclic stretching. The fibroblast cells sense the structural shape of the substrate that they are adhered to which helps determine their cell shape, function, and spreading. "Simultaneous in vitro work showed that topographic features affect cellular alignment, direction of proliferation, cellular attachment, growth rate, metabolism, and cytoskeleton arrangement." When the dermal fibroblasts were cultured on substrates with grooves, the fibroblasts aligned along the grooves. It was shown that increased groove depth increased the rate of fibroblast orientation. With the V-groove topography, the fibroblasts were more clearly aligned because of the increased groove depth. It was shown that increased groove depth was more important in the alignment of fibroblasts than the spacing between the grooves. The grooves perpendicular to the direction of stretch had a better fibroblast alignment. On the square groove substrate the fibroblasts were flat and they protruded to the bottom of the grooves. On the controlled smooth substrates, the fibroblasts spread out randomly and they did not produce any kind of alignment.

When the cells are under the influence of cyclic stretch, the fibroblasts tend to orient themselves perpendicular to the direction of stretch. Also, the expressions of the main molecules in cell-matrix adhesion (collagen type 1, fibronectin, and α1 and β1 integrins) were affected by cyclic stretch. The concentration of β1-integrins and collagen type 1 increased with cyclic stretch. Alternatively, α1-integrin concentration decreased with increased cyclic stretch.

This experiment showed that fibroblasts first change their shape according to the topography of the substrate, while the secondary role is mechanical forces. The cells reaction to the mechanical forces can take place only after the cell has adhered, established a connective arrangement (integrins, cytoskeleton, and ECM), and spread out. These components are important for the fibroblast cells so they will have support for mechanical forces. Also, cell spreading helps turn off apoptosis. I found this topic interesting to find out that cells first respond to the topography of the substrate then to the mechanical forces.

http://www.ncbi.nlm.nih.gov/pubmed/16110493