Rectified Cell Migration on Saw-Like Micro-Elastically Patterned Hydrogels with Asymmetric Gradient Ratchet Teeth

To control cell motility is one of the essential technologies for biomedical engineering. To establish a methodology of the surface design of elastic substrate to control the long-range cell movements, here we report a sophisticated cell culture hydrogel with a micro-elastically patterned surface that allows long-range durotaxis. This hydrogel has a saw-like pattern with asymmetric gradient ratchet teeth, and rectifies random cell movements. Durotaxis only occurs at boundaries in which the gradient strength of elasticity is above a threshold level. Consequently, in gels with unit teeth patterns, durotaxis should only occur at the sides of the teeth in which the gradient strength of elasticity is above this threshold level. Therefore, such gels are expected to support the long-range biased movement of cells via a mechanism similar to the Feynman-Smoluchowski ratchet, i.e., rectified cell migration. The present study verifies this working hypothesis by using photolithographic microelasticity patterning of photocurable gelatin gels. Gels in which each teeth unit was 100-120 µm wide with a ratio of ascending:descending elasticity gradient of 1:2 and a peak elasticity of ca. 100 kPa supported the efficient rectified migration of 3T3 fibroblast cells. In addition, long-range cell migration was most efficient when soft lanes were introduced perpendicular to the saw-like patterns. This study demonstrates that asymmetric elasticity gradient patterning of cell culture gels is a versatile means of manipulating cell motility.