Spatial distribution of cells and
their interactions between neighboring
cells in native microenvironments are of fundamental importance in
determining cell fate decisions such as migration, growth, and differentiation.
Controlling the spatial distribution of different cell types in defined
geometries can replicate these native environments, which can be a
useful model for several studies. While spatiotemporal control over
multiple cell arrangements is required to achieve the complex tissue
architecture, unfortunately, conventional cell patterning techniques
usually allow only single patterning with a single cell type. In the
present study, we introduce a simple lithographic method to pattern
multiple cell types in a spatially controlled manner by utilizing
the biophysical cues present at the corners of the patterned geometry.
By fabricating micropatterns of different shapes, we demonstrate how
the cell can be constrained to pattern along the corners of patterned
geometries owing to the presence of topographical cues, leaving empty
voids in the center that can be further utilized for patterning a
second cell type. We also demonstrate that the cell alignment along
the pattern is a dynamic process and the cells migrate from a more
uniform cell-adhesive region toward the topographical cues. The cytoskeleton
arrangement was geometry-dependent, which was confirmed through a
series of in vitro evaluations, such as scanning
electron microscopy and fluorescence microscopy. These findings have
not only helped us in exploring the importance of these cues in guiding
the cell fate but have also allowed us to develop a technique, which
self-patterns the cells without any expensive exogenous cues and can
be used as a model protocol to eventually organize cells into a specific
pattern with micron-scale precision in vitro.