THE EFFECT OF NANOFIBER DIAMETERS ON INTEGRIN REGULATED FAK-SRC SIGNALLING AND MIGRATION RATES OF HUMAN MESENCHYMAL STEM CELLS

Open Access
Author:
Mcculloch, Mary Elizabeth
Area of Honors:
Biomedical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Justin Lee Brown, Thesis Supervisor
  • William O Hancock, Honors Advisor
Keywords:
  • FAK
  • SRC
  • Tissue Engineering
  • hMSCs
  • migration
  • Focal adhesions
Abstract:
Nanofibers play a significant role in modulating tissue growth. 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. 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 is involved with cell attachment and migration and Src is an important regulator of differentiation and proliferation. This research aims to characterize migration of Human Mesenchymal Stem Cells (hMSCs) on poly(methyl methacrylate) (PMMA) nanofibers of varying diameters. 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 length was also measured. This study shows FAK and Src concentrations differed for substrates of nanofibers with varying diameters. Migration rates were found to be significantly different on nanofibers of different mean diameters. A decrease in pFAK-576/577 resulted in faster migrating cells and ultimately revealed a dependency on Src-416 for activation.