Passive control of cell locomotion using micropatterns: the effect of micropattern geometry on the migratory behavior of adherent cells

Abstract

Directed cell migration is critical to a variety of biological and physiological processes. Although simple topographical patterns such as parallel grooves and three-dimensional post arrays have been studied to guide cell migration, the effect of the dimensions and shape of micropatterns, which respectively represent the amount and gradient of physical spatial cues, on cell migration has not yet been fully explored. This motivates a quantitative characterization of cell migration in response to micropatterns having different widths and divergence angles. The changes in the migratory (and even locational) behavior of adherent cells, when the cells are exposed to physical spatial cues imposed by the micropatterns, are explored here using a microfabricated biological platform, nicknamed the "Rome platform". The Rome platform, made of a biocompatible, ultraviolet (UV) curable polymer (ORMOCOMP), consists of 3 μm thick micropatterns with different widths of 3 to 75 μm and different divergence angles of 0.5 to 5.0°. The migration paths through which NIH 3T3 fibroblasts move on the micropatterns are analyzed with a persistent random walk model, thus quantifying the effect of the divergence angle of micropatterns on cell migratory characteristics such as cell migration speed, directional persistence time, and random motility coefficient. The effect of the width of micropatterns on cell migratory characteristics is also extensively investigated. Cell migration direction is manipulated by creating the gradient of physical spatial cues (that is, divergence angle of micropatterns), while cell migration speed is controlled by modulating the amount of them (namely, width of micropatterns). In short, the amount and gradient of physical spatial cues imposed by changing the width and divergence angle of micropatterns make it possible to control the rate and direction of cell migration in a passive way. These results offer a potential for reducing the healing time of open wounds with a smart wound dressing engraved with micropatterns (or microscaffolds).

Poly-l-arginine based materials as instructive substrates for fibroblast synthesis of collagen

“…Cells cultured on TCPS were in the middle of these regions with a P of 60 min and an S of 0.18 mm/min. This compares well with other literature values of~0.2 mm/min for NIH/3T3 cells [41],~0.17 mm/min for primary fibroblasts [42], and directional persistence of~40 min for secondary fibroblasts [43].…”

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.…”

“…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.…”

Versatile method to generate multiple types of micropatterns

“…Micropatterning techniques have become an established tool for researchers interested in single-cell functions and dynamics [1][2][3][4][5][6][7] and the collective behavior of small cell assemblies and tissues [8][9][10] . Their significance for today's cell science arises from the fact that they provide direct control over the shape and functionality of the cell's environment on a microscopic scale.…”