Topographic Cues Regulate Collective Cell Dynamics in Curved Nano/Microgrooved Tubular Microchannels

Abstract

Physical properties of the extracellular matrix, such as topography and curvature, regulate collective epithelial behaviors. However, the interplay between these geometric factors on collective migration is not well understood. In this study, we investigate the effects of topographic cues on a curved surface on collective epithelial migration within tubular microchannels with an inner diameter of 100 µm. These tubular microchannels feature circumferential or longitudinal micro- and nano-grooves fabricated by two-photon polymerization three-dimensional printing and micro-molding techniques. Live cell microscopy records the collective migration of the GFP-labeled epithelial cell into the microchannel with each topographical design. We utilized a single-cell behavior analysis for the tracked time-dependent cell position data to visualize and quantify complex cell migration. Results show that longitudinal grooves (800 nm and 4 μm) enhanced cell migration, but circumferential grooves did not significantly enhance cell migration. This indicates that curvature rather than topography dominates migration at the microtubule scale. These findings provide insights into the interplay between curvature, microscale structure, and cell behaviors and suggest the potential to control cell behaviors by manipulating the structure and topographic cues with their local microenvironments.