(227af) Microrheological Characterization of Cell-Material Interactions during 3D hMSC Migration

Designing scaffolds that mimic aspects of the extracellular matrix and provide a 3D microenvironment that can be remodeled by cells during migration has been an area of growing interest with applications in wound healing, tissue engineering and stem cell expansion. Although such materials provide an initially well-defined microenvironment for the cells, little is known about how cells interact with and permanently remodel the matrix. The lack of quantitative and predictable information about this process has limited advances in biomaterial design that can manipulate and control cellular motility. To bridge this gap, we use microrheology to characterize a matrix metalloproteinase (MMP) degradable hydrogel both temporally and spatially during 3D human mesenchymal stem cell (hMSC) encapsulation focusing on the region directly around the cell, the pericellular region, during migration. Temporally, we quantify the change in the scaffold rheological properties as the cell degrades the material past the critical gel-sol transition. Spatially, we measure the change in material properties as a function of the distance away from the cell. We observe that the cell degrades a gradient into the material with the largest degradation furthest from the cell. For motility hMSCs must adhere to the network and use cytoskeletal tension to move. Therefore, we measure cellular adhesion to the material directly under the cell prior to motility while MMPs are secreted to degrade the scaffold to enable facile motility. This degradation pattern is also measured when cells are treated with a myosin II inhibitor, which inhibits cells from pulling on the scaffold. This work provides a foundation to quantitatively understand dynamic environments that cells reengineer during basic processes enabling design of tunable synthetic materials to enhance and direct cell motility.