Mammalian cells redirect their movement in response to changes in the physical properties of their extracellular matrix (ECM) adhesive scaffolds, including changes in available substrate area, shape, or flexibility. Yet, little is known about the cell's ability to discriminate between different types of spatial signals. Here we utilize a soft-lithography-based, microcontact printing technology in combination with automated computerized image analysis to explore the relationship between ECM geometry and directional motility. When fibroblast cells were cultured on fibronectin-coated adhesive islands with the same area (900 micrometers2) but different geometric forms (square, triangle, pentagon, hexagon, trapezoid, various parallelograms) and aspect ratios, cells preferentially extended new lamellipodia from their corners. In addition, by imposing these simple geometric constraints through ECM, cells were directed to deposit new fibronectin fibrils in these same corner regions. These data indicate that mammalian cells can sense edges within ECM patterns that exhibit a wide range of angularity and that they use these spatial cues to guide where they will deposit ECM and extend new motile processes during the process of directional migration.
This paper reports a simple and versatile technique for generating structures on the surfaces of poly(dimethylsiloxane) (PDMS), approximately sinusoidal waves with periods between 0.1 and 10 μm, and the
use of these structures to study cell contact guidance. The features are generated by stretching PDMS
slabs mechanically, oxidizing them in an oxygen plasma, and allowing them to relax. These surface features
are similar to photolithographically fabricated grooves that have traditionally been used to investigate
cell contact guidance, although their edges are rounded rather than angular. Bovine capillary endothelial
cells align and elongate on these features. The morphology and cytoskeletal structure of the aligned cells
are similar to those of cells described in previous studies of contact guidance on surfaces with other types
of topography. These observations and comparisons indicate that sharp edges in the features defining the
grooves are not essential in eliciting contact guidance. This technique provides a method for fabricating
microfeatures for the studies of the interactions between cells and their environment that does not require
a cleanroom or access to photolithographic tools.
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