Directing cell migration in continuous microchannels by topographical amplification of natural directional persistence

Abstract

Discrete micropatterns on biomaterial surfaces can be used to guide the direction of mammalian cell movement by orienting cell morphology. However, guiding cell assembly in three-dimensional scaffolds remains a challenge. Here we demonstrate that the random motions of motile cells can be rectified within continuous microchannels without chemotactic gradients or fluid flow. Our results show that uniform width microchannels with an overhanging zigzag design can induce polarization of NIH3T3 fibroblasts and human umbilical vein endothelial cells by expanding the cell front at each turn. These continuous zigzag microchannels can guide the direction of cell movement even for cells with altered intracellular signals that promote random movement. This approach for directing cell migration within microchannels has important potential implications in the design of scaffolds for tissue engineering.

Cells as Active Particles in Asymmetric Potentials: Motility under External Gradients

“…The vectors indicated that net motion was isotropic and random on flat surfaces, whereas it was rectified toward the positive y axis on the ratchet pattern. Previous gradient-free strategies relied on cell confinement, either chemical (12)(13)(14)(15) or physical (16)(17)(18). However, here we show that cells on an asymmetric topographical pattern, with no restriction in adhesiveness or physical confinement, moved in the direction imposed by the features of the ratchet itself.…”

“…Geometrical asymmetries in the pattern design amplified natural differences in lamellipodia activity at the front and the rear of a polarized cell, leading to directed motion (12)(13)(14)(15)17,18). Because we used homogeneous fibronectin coatings and topographical patterns smaller than the cell size and of a moderate height (35), we did not restrict cell migration in any direction.…”

“…Previous studies achieved biased cell motion by asymmetric patterns, either chemical (12)(13)(14)(15) or physical (13,(16)(17)(18), that induced cell polarization by means of confining cells and restricting their motion to one-dimensional. Geometrical asymmetries in the pattern design amplified natural differences in lamellipodia activity at the front and the rear of a polarized cell, leading to directed motion (12)(13)(14)(15)17,18).…”

“…Furthermore, several studies report directional cell motion in vitro by imposing asymmetric cues to the cells. In addition to asymmetric one-dimensional paths, both chemical (12)(13)(14)(15) and topographical (16)(17)(18), adhesive (19) and stiffness gradients (20) also direct cell migration. On these substrates, cell motion is often understood to be directional-with a persistent trajectory along the same direction of an axis-because the cell symmetry is broken by the external cues.…”

Topography Design Concept of a Tissue Engineering Scaffold for Controlling Cell Function and Fate Through Actin Cytoskeletal Modulation

“…5B). 125,126 In cells on a micro-/nano-grooved structure, actin filaments and vinculinrich focal adhesions align with the longer axis of the grooves. This effect causes various cells, such as epithelial, endothelial, glial cells, fibroblasts, osteoblasts, and neutrophils, to align 73,96,120,121 and migrate 4,121,123,124 along the grooves.…”