Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells

Cheng Zhang, Hongyuan Zhu, Xinru Ren, Bin Gao, Bo Cheng, Shaobao Liu, Baoyong Sha, Zhaoqing Li, Zheng Zhang, Yi Lv, Haohua Wang, Hui Guo, Tian Jian Lu, Feng Xu, Guy M. Genin and Min Lin ()
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Cheng Zhang: Xi’an Jiaotong University
Hongyuan Zhu: Xi’an Jiaotong University
Xinru Ren: Xi’an Jiaotong University
Bin Gao: Second Affiliated Hospital of Air Force Military Medical University
Bo Cheng: Xi’an Jiaotong University
Shaobao Liu: Nanjing University of Aeronautics and Astronautics
Baoyong Sha: Xi’an Medical University
Zhaoqing Li: Xi’an Jiaotong University
Zheng Zhang: Xi’an Jiaotong University
Yi Lv: The First Affiliated Hospital of Xi’an Jiaotong University
Haohua Wang: The First Affiliated Hospital of Xi’an Jiaotong University
Hui Guo: The First Affiliated Hospital of Xi’an Jiaotong University
Tian Jian Lu: Nanjing University of Aeronautics and Astronautics
Feng Xu: Xi’an Jiaotong University
Guy M. Genin: Xi’an Jiaotong University
Min Lin: Xi’an Jiaotong University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell’s mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed “mechanical memory” in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems.

Date: 2021
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DOI: 10.1038/s41467-021-26454-x

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