Keywords: microrheology, cell-material interactions
Summary:Cells do not simply reside within materials they actively reengineer them. Due to this active remodeling, the microenvironments within our body, especially during wound healing and tissue regeneration, are dynamic and adaptable. These native environments present both physical and chemical cues to cells to manipulate cellular processes, such as motility, but the combination and individual signals remain largely unknown. To combat this problem, synthetic hydrogel scaffold have been designed to serve as blank slates where physical and chemical cues can be controllably presented to cells encapsulated within them in 3D. Although these biomaterials scaffolds provide initially well-defined microenvironments for 3D culture of cells, less is known about the changes that occur over time, especially local matrix remodeling that can play an integral role in directing cell behavior. We use microrheology as a quantitative tool to characterize dynamic cellular remodeling of peptide-functionalized poly(ethylene glycol) (PEG) hydrogels that degrade in response to cell-secreted matrix metalloproteinases (MMPs). Multiple particle tracking microrheology measures the Brownian motion of probe particles embedded within the material. These measurements are related to material properties using the Generalized Stokes-Einstein Relation. This technique allows measurement of spatial changes in material properties during migration of encapsulated cells and has a sensitivity that identifies regions where cells simply adhere to the matrix, as well as the extent of local cell remodeling of the material through MMP-mediated degradation. Collectively, these microrheological measurements provide insight into microscopic, cellular manipulation of the pericellular region that gives rise to macroscopic tracks created in scaffolds by migrating cells. This quantitative and predictable information will benefit the design of improved biomaterial scaffolds for medically relevant applications.