Publication date: 25th July 2016
Cell migration plays a critical role in a large number of physiological and pathological processes in the body, such as tissue development and wound healing. Moreover, cell migration is essential in scaffold-based tissue engineering applications to allow sufficient cell colonization throughout the whole scaffold. It is well known that cell migration can be triggered and directed by changes in the mechanical or chemical properties of the cell’s microenvironment. However, the knowledge on how cell migration is influenced by the geometrical properties of the cell’s environment is still limited. A deeper insight in how cells migrate in response to geometrical cues of different length scales is therefore needed to understand the role of the architecture of the extracellular environment as a cell-instructive parameter in health and disease.
In this study we explore the impact of geometry on cell migration on 2 competing length scales. We developed a method to deposit isotropic and anisotropic fibrillar collagen networks on cylindrical substrates with radii of 125- 2500 µm created in PDMS via a molding process. Using this method, we systematically varied the mesoscale-curvature of the substrate in combination with nanoscale geometrical cues provided by the collagen fibers. We monitored the migration of human mesenchymal stem cells (hMSCs) on these structures using confocal time-lapse imaging and analysed the migration speed, migration direction and persistence length. Our data reveals that at low surface curvatures (on large radius cylinders) cells align and migrate along the direction of the aligned collagen. However, with increasing curvature (smaller radius cylinders), a second mesoscale guiding-mechanism was observed where cells tend to align along the cylinder axis. The results indicate that cell migration is controlled by the combined, and sometimes competing, effect of contact guidance by the small, aligned collagen fibrils and surface-curvature guidance by structures much larger than the cell size. The knowledge gained from this study could be of relevance for the design of cell-instructive biomaterials, e.g. in the field of tissue engineering, but also for a better understanding on organogenesis and disease pathogenesis.
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