The extracellular matrix (ECM) exhibits rich 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. Dissecting these biochemical and biomechanical cues provided by the ECM is instrumental in the understanding of many biological processes. Over the past 2 decades, micropatterning and nanopatterning toolkits that are used to engineer cell-substrate interfaces have emerged, rapidly expanded and widely used among bioengineers and biologists for the study of cell biology. Among these studies, surface topography has been widely recognized to participate in controlling cellular functions including cell adhesion, migration, proliferation, polariz...[ Read more ]

The extracellular matrix (ECM) exhibits rich 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. Dissecting these biochemical and biomechanical cues provided by the ECM is instrumental in the understanding of many biological processes. Over the past 2 decades, micropatterning and nanopatterning toolkits that are used to engineer cell-substrate interfaces have emerged, rapidly expanded and widely used among bioengineers and biologists for the study of cell biology. Among these studies, surface topography has been widely recognized to participate in controlling cellular functions including cell adhesion, migration, proliferation, polarization and differentiation. However, very few studies have evaluated how surface topography affects epithelial tissue-like morphogenesis and how surface topography modulates the distribution of membrane proteins that are normally thought not associated with the adhesion complex. Meanwhile, studying cell behavior in a defined microenvironment by using surface microengineering tools offers tremendous advantage over traditional uncontrolled methods. This direction is also inadequately explored especially in the study of cell mechanics in a controlled microenvironment. This work offers a peek at the potential role of surface topography in the aforementioned aspects. Specifically, the effect of substrate nanotopography on the tissue-like morphogenesis of several types of epithelial cells was examined. We demonstrated that substrate nanotopography, one of the first physical cues detected by cells, can by itself induce epithelial cyst formation. We further explored the possibility of generating probe-accessible, size-controllable epithelial cysts by using micropatterning and combined it with atomic force microscopy to characterize the cyst mechanics. By using this platform, we estimated the elasticity of the cyst monolayer and showed that the presence of a luminal space influences cyst mechanics substantially, which could be attributed to polarization and tissue-level coordination. More interestingly, the results from force-relaxation experiments showed that the cysts also displayed tissue-level poroelastic and power-law characteristics. Last but not least, we evaluated the potential role of a membrane protein, ANO1 (anoctamin 1), in membrane curvature sensing by subjecting exogenously overexpressed ANO1 to various membrane curvatures that are externally induced by substrate topography such as micropillar and microgroove patterns. Markedly, membrane distribution of ANO1 was profoundly modulated by substrate topography as characterized by the clustering at positively curved membrane regions. Analysis of the clustering dynamics revealed that ANO1 potentially associates with adhesion complexes to form large-scale assemblies.