The Pennsylvania State University Schreyer Honors College Department of Biomedical Engineering the Effect of Nanofiber Diameters on Integrin Regulated Fak-src Signalling and Migration Rates of Human Mesenchymal Stem Cells

نویسندگان

  • MARY ELIZABETH MCCULLOCH
  • Justin Brown
  • William Hancock
چکیده

Nanofibers play a significant role in modulating tissue growth.[1][2][3] Applications include nerve regeneration, wound healing, hernia repair, and repair of musculoskeletal tissues. Cells sense environments via signal transduction pathways, which can lead to changes in cell shape, proliferation rates, gene expression, and differentiation.[4] Integrins are a type of protein that exists on the cell's surface and initiate intracellular signaling and play a major role in the adhesion of cells to a surface. These integrins utilize inside-out as well as outside-in communication and are the mediator of the cell's interaction with surrounding extracellular matrix. Integrins activate other signaling proteins, including Focal Adhesion Kinase(FAK) and Src which exist in many phosphorylation states. FAK and Src act in a mutual activation to amplify existing signal for cellular migration processes. This research aims to characterize migration of Human Mesenchymal Stem Cells (hMSCs) on poly(methyl methacrylate) (PMMA) nanofibers of five different diameters ranging from 100nm – 1200nm. Relative FAK and Src concentrations of hMSCs were quantified on nanofiber scaffolds of varying diameters. Migration rates across each diameter of nanofiber were also observed at two different time points and focal adhesion lengths were measured. This study shows FAK and Src concentrations differed for substrates of nanofibers with different diameters. Migration rates were found to be significantly different on nanofibers of different mean diameters. A decrease in pFAK-576/577 concentration resulted in faster migrating cells and ultimately revealed a dependency on Src-416 for activation, whose decrease also lead to faster migration.

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تاریخ انتشار 2016