Micropatterned substrates: Tools for studying cell motility and aiding rational drug design

Abstract

We have developed a novel class of cell biology tools for the quantification of cytoskeletal organization and dynamics in populations of cancerous cells with low variability. Anisotropic Solid Microetching (ASoMiC) was used to constrain cells onto transparent microislands and subsequently imaged. This methodology creates a unique platform for studying cell motility and identifying therapeutic targets.Triangular microislands spatially segregate cytoskeletal components and allow for study of microtubule (MT) growth trajectories in defined geometric confines. We show that growing MTs are targeted towards focal adhesions (FAs). RNAi studies reveal that myosin IIA dependent f‐actin bundles are integral to this process. Since MT targeting of FAs is important in metastasizing cancer cells, this system can be used to identify new cancer therapeutic targets.To study cell motility, we used micropatterned linear tracks to constrain cells to 1‐D. We found that metastatic cells were “superdiffusive” vs. “diffusive” non‐metastatic cells. This quantitative description of a cell's motility leads to the systematic characterization of metastatic potential and response to therapeutic agents.ASoMiC allows the study of cytoskeletal organization and dynamics of cancerous cells with minimal cell‐to‐cell variability. These systems provide a platform for the study and manipulation of the cytoskeletal organization.Funding: NIH Award 1R21CA137707‐01