Cell migration through biomimetic hydrogel scaffolds
Gobin, Andrea Samantha
West, Jennifer L.
Doctor of Philosophy
Cell migration is an essential step during processes such as embryonic development, wound healing, angiogenesis, and cancer metastasis. Migration is a complex integration of cellular adhesion to its substratum, reorganization of the cytoskeleton, proteolysis and remodeling of surrounding extracellular matrix (ECM), and activation and regulation of chemical signaling by growth factors and other mitogenic cues. These cooperative mechanisms enable a cell to move to its target to perform its function, whether to repair injured tissue, fight infections, or build new blood vessels. The main objective of this research is to study mechanisms of cell migration within a biomimetic hydrogel system. Because of the complexity of the ECM, studying cell migration in ECM derivatives or even single components of the ECM can make it difficult to decipher the importance of each factor involved. In addition, the ECM imposes a spatial barrier to cells. For migration, the cells must not only interact with matrix adhesive ligands for force generation, but also develop strategies to overcome biomechanical resistance imposed by the matrix. Thus, the biomimetic hydrogel system developed can provide the mechanical support, adhesion ligands, degradation sequences, and other signals, so that a cell can migrate. This system will provide tight control over many experimental parameters and minimize nonspecific cell-material interactions. Hence the aim of the hydrogel system is to stimulate an active interaction between the synthetic polymer and the biological environment. The biomimetic hydrogels are photopolymerizable hydrogels based on acrylated derivates of polyethylene glycol. This material contains proteolytically degradable peptide sequences, targeted for specific enzymes involved in cell migration, in the polymer backbone. Cell adhesion peptides are also grafted into the hydrogels during photopolymerization to promote interaction with specific cell surface receptors. Other bioactive signals, such as growth factors, can also be grafted into the network during photopolymerization. Thus a single hydrogel material can contain several different proteolytically sensitive segments, many cell adhesion ligands and various growth factors, allowing for one to mimic many properties of the ECM. This hydrogel system is used to assess cell migration mechanisms by controlling the identity and availability of bioactive signals presented to the cells and studying their affects.