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. 2019 Feb 6;9:1507. doi: 10.1038/s41598-018-37804-z

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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IPKB analysis of relationships among upregulated genes on silk film topography. (1) Cell surface integrin receptors sense biophysical cues provided by surface topographical patterns on silk (blue texts) which leads the the activation of key regulators of actin remodeling and recruitment of focal adhesion kinase (dark black text). (2) FAK then induces the activation of RAS superfamily of small GTPases (red texts), (3) leading to the activation of NOTCH signaling pathway (green texts) and (4) ERK/MAPK (extracellular signal-regulated kinases/mitogen-activated protein kinases) signaling pathway (purple texts). (5) The activation of these pathways leads to transcriptional changes (grey texts) related to cell proliferation and differentiation.