Probing the Dose-Dependent Effect of Migration Stimulating Factor-Like Drug on Fibroblast Migration using Optical Tweezers

Abstract

Human dermal fibroblast migration is one of the most important step in wound healing. Normal and impaired wound healing has long been recognized to be coordinated by the soluble regulatory molecules and the insoluble extracellular matrix. Biological growth factors tested as wound care therapies include proteins and analogues that may function as wound healing cytokines, including epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). However, all the above growth factors are applied at relatively high concentrations over extended periods of time. Recently, migration stimulating factor (MSF) has been reported to stimulate the migration of fibroblasts, epithelial and endothelial cells; in addition, MSF is expected to induce cell motility at a low dose concentration. We propose an experimental approach to establish a dose dependent relationship with human dermal fibroblast cell at the single cell level. Our idea is that using polystyrene beads coated with different concentrations of migration stimulating factor-like small molecule MM-IGD-Az-2 as a point source of a chemoattractant to locally stimulate human dermal fibroblast cells CCD-996SK, where the cell response is mediated by the binding of the MM-IGD-Az-2 to integrin αvβ3 receptor. We then apply high-resolution optical tweezers system to conduct spatial and temporal regulation of cell locomotion at the single-cell level, where optically trapped bead is coated with the chemoattractant MM-IGD-Az-2. We anticipate the proposed approach based on nano-biomedical technologies, together with the platform at single-cell level could be applied to build a methodology for wound healing behavior at the cellular level.