The physical properties and topological cues of a micro/nanopattern affect both cell functional activity and tissue regeneration. In this study, we developed a bioinspired approach to fabricate a microconical pattern mimicking the wing structure of beetle Coleoptera. The bioinspired micropattern with multistructural hierarchy was first screened from eight representative insect families of coleopteran. Then, we fabricated a conical micropattern through a two-step nanoimprint lithography technology. We found that human adult fibroblast cells on the bioinspired micropattern substrate had a larger spread area and higher proliferation efficiency than those on flat polydimethylsiloxane. The physical properties and topological cues affect cell functional activity. Through in situ cell motility tracking, we found that conical pillars provided specific attachment points as a mechanotransduction foundation for cell attachment to spread. The holding pillar on the bioinspired surface facilitates the actin and vimentin filament assembly into mature straightened bundles in the cytoplasm. This bioinspired substrate is transparent, flexible, and easy to fabricate. Moreover, it provides a novel in situ platform to investigate cell behaviors.

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Protein kinase-mediated phosphorylation plays a critical role in many biological processes. However, the identification of key regulatory kinases is still a great challenge. Here, we develop a trans-omics-based method, central kinase inference, to predict potentially key kinases by integrating quantitative transcriptomic and phosphoproteomic data. Using known kinases associated with anti-cancer drug resistance, the accuracy of our method denoted by the area under the curve is 5.2% to 29.5% higher than Kinase-Substrate Enrichment Analysis. We further use this method to analyze trans-omic data in hepatocyte maturation and hepatic reprogramming of human dermal fibroblasts, uncovering 5 kinases as regulators in the two processes. Further experiments reveal that a serine/threonine kinase, PIM1, promotes hepatic conversion and protects human dermal fibroblasts from reprogramming-induced ferroptosis and cell cycle arrest. This study not only reveals new regulatory kinases, but also provides a helpful method that might be extended to predict central kinases involved in other biological processes.