Adaptive liquid interfaces induce neuronal differentiation of mesenchymal stem cells through lipid raft assembly

Xiaofang Jia (), Jingwen Song, Wenyan Lv, Jonathan P. Hill, Jun Nakanishi () and Katsuhiko Ariga ()
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Xiaofang Jia: Shenzhen Campus of Sun Yat-sen University
Jingwen Song: National Institute for Materials Science (NIMS)
Wenyan Lv: Shenzhen Campus of Sun Yat-sen University
Jonathan P. Hill: National Institute for Materials Science (NIMS)
Jun Nakanishi: National Institute for Materials Science
Katsuhiko Ariga: National Institute for Materials Science (NIMS)

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Stem cells and their microenvironment interact cooperatively to dictate their fates. Biomaterials are dynamically remodeled by stem cells, and stem cells sense and translate the changes into cell fate decisions. We have previously reported that adaptive biomaterials composed of fibronectin inserted into protein nanosheets at a liquid interface enhance neuronal differentiation of human mesenchymal stem cells (hMSCs). However, we could not decouple clearly the effect of ligand density from that of fibrillary structure on cellular function and fate. Here we present an adaptive biomaterial based on two-dimensional networks of protein nanofibrils at a liquid–liquid interface. Compared with flat protein nanosheets, this biomaterial enhances neuronal differentiation of hMSCs through a signaling mechanism involving focal adhesion kinase. Lipid raft microdomains in plasma membrane are found to play a central role in which hMSCs rapidly adapt to the dynamic microenvironment at the fluid interface. Our finding has substantial implications for regenerative medicine and tissue engineering.

Date: 2022
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DOI: 10.1038/s41467-022-30622-y

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