Abstract
The extracellular matrix (ECM) exhibits tissue-specific topography and composition and plays a crucial role in initiating the biochemical and biomechanical signaling required for organizing cells into distinct tissues during development. How single cells assemble into structures featuring specific shapes in response to external cues is poorly understood. We examined the effect of substrate nanotopography on the morphogenesis of several types of epithelial cells and found that in response to the topography, Calu-3 and MDCK-II cells formed organoids that closely resemble their morphology in vivo. This finding represents the first demonstration that substrate nanotopography, one of the first physical cues detected by cells, can by itself induce epithelial tissue-like organization. Our results provide insights, in terms of a new aspect of ECM topography, into the design of future tissue-engineering systems and the study of mechanosignaling in the epithelium during normal development and tumor progression.
Highlights
The extracellular matrix (ECM) exhibits tissue-specific topography and composition and plays a crucial role in initiating the biochemical and biomechanical signaling required for organizing cells into distinct tissues during development
We examined the effect of substrate nanotopography on the morphogenesis of several types of epithelial cells and found that in response to the topography, Calu-3 and MDCK-II cells formed organoids that closely resemble their morphology in vivo
Using scanning electron microscopy (SEM), we verified the geometry and dimensions of randomly aligned nanograss featuring a high aspect ratio (.10) (Fig. 1). We developed this design based on 2 considerations: (1) The effect of contact guidance on epithelial morphogenesis can be minimized when nanospikes are arranged stochastically and isotropically in order to locally restrict cell spreading, migration, and proliferation along the horizontal plane[2,5,6,7,10]; (2) Intense, dynamic, and reciprocal interactions between cells and topographic patterns can be achieved when the accessibility and flexibility of nanograss are controlled by modifying nanograss density and aspect ratio[11,12,13,14]
Summary
The extracellular matrix (ECM) exhibits tissue-specific topography and composition and plays a crucial role in initiating the biochemical and biomechanical signaling required for organizing cells into distinct tissues during development. We examined the effect of substrate nanotopography on the morphogenesis of several types of epithelial cells and found that in response to the topography, Calu-3 and MDCK-II cells formed organoids that closely resemble their morphology in vivo This finding represents the first demonstration that substrate nanotopography, one of the first physical cues detected by cells, can by itself induce epithelial tissue-like organization. Over the past 2 decades, methods of generating epithelial organoids have been developed and they mainly involve providing cells with a 3D culture environment in which chemical cues provided by ECM proteins induce rapid epithelial polarization and tissue organization[3,4] Another critical cue that the ECM could present is a rich 3D surface topography at the nano and micro scales; this topography has been widely recognized to participate in controlling cellular functions including cell adhesion, migration, proliferation, and differentiation. Our results clearly reveal the crucial role that ECM topography could play in dictating epithelial morphogenesis and cell fate
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