Repositioning of cells by mechanotaxis on surfaces with micropatterned Young's modulus

Abstract: Adherent cells are strongly influenced by the mechanical aspects of biomaterials, but little is known about the cellular effects of spatial variations in these properties. This work describes a novel method to produce polymeric cell culture surfaces containing micrometer-scale regions of variable stiffness. Substrates made of acrylamide or poly-(dimethylsiloxane) were patterned with 100- or 10-m res-olution, respectively. Cells were cultured on fibronectin-coated acrylamide having Young’s moduli of 34 kPa and 1.8 kPa, or fibronectin-coated PDMS having moduli of 2.5 MPa and 12 kPa. Over several days, NIH/3T3 cells and bovine pulmonary arterial endothelial cells accumulated preferen-tially on stiffer regions of substrates. The migration, not proliferation, of cells in response to mechanical patterning (mechanotaxis) was responsible for the accumulation of cells on stiffer regions. Differential remodeling of extracellular matrix protein on stiff versus compliant regions was ob-served by immunofluorescence staining, and may have been responsible for the observed mechanotaxis. These results suggest that mechanically patterned substrates might pro-vide a general means to study mechanotaxis, and a new approach to patterning cells. © 2003 Wiley Periodicals, Inc