The effect of surface topography on cell shape and early ERK1/2 signaling in macrophages; linkage with FAK and Src†

Division of Oral Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London,Ontario, N6A 5C1, CanadaReceived 27 July 2012; revised 8 October 2012; accepted 22 October 2012Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.34509Abstract: Implant surface topography can modulate macro-phage behavior during wound healing by the production ofproinflammatory cytokines. This study investigated the activa-tion of FAK, Src, and ERK1/2 signaling intermediates of theproinflammatory ERK1/2 pathway in RAW 264.7 macrophagesin response to polished (P), coarse-grit-blasted (B), acid etched(E), and grit-blasted and etched (SLA) surface topographies. Inaddition, the effects of these topographies on cell spreading,vinculin organization, and viability were determined. Macro-phages on the SLA surface changed from predominantly well-spread cells to ones with a more spherical morphology overtime. In contrast, macrophages on the P surface changed frombeing predominantly spherical cells to well spread. The mor-phological changes were associated with changes in the distri-bution of vinculin. The overall patterns of the pFAK, pSrc,pERK1/2 levels as well as pERK1/2 nuclear translocation associ-ated with cell shape with greater activation being seen with amore spread morphology. These results suggest that surfacetopography differentially activates signaling pathways thataffect cell function and raise the possibility that topographiescan be designed to optimize desired cell responses.