3D micropattern force triggers YAP nuclear entry by transport across nuclear pores and modulates stem cells paracrine  

作　　者：Yan Li Zhenyu Zhong Cunjing Xu Xiaodan Wu Jiaqi Li Weiyong Tao Jianglin Wang Yingying Du Shengmin Zhang 

机构地区：[1]Advanced Biomaterials and Tissue Engineering Center,Huazhong University of Science and Technology,Wuhan 430074,China [2]Department of Biomedical Engineering,Huazhong University of Science and Technology,Wuhan 430074,China [3]Research Base of Regulatory Science for Medical Devices,National Medical Products Administration&Institute of Regulatory Science for Medical Devices,Huazhong University of Science and Technology,Wuhan 430074,China

出　　处：《National Science Review》2023年第8期174-187,共14页国家科学评论（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(31430029,82130061 and 32171331);the Young Elite Scientist Sponsorship Program byChina Association for Science and Technology(YESS20200077);the Natural Science Foundation of Hubei Province(2021CFB609).

摘　　要：Biophysical cues of the cellular microenvironment tremendously influence cell behavior by mechanotransduction.However,it is still unclear how cells sense and transduce the mechanical signals from 3D geometry to regulate cell function.Here,the mechanotransduction of human mesenchymal stem cells(MSCs)triggered by 3D micropatterns and its effect on the paracrine of MSCs are systematically investigated.Our findings show that 3D micropattern force could influence the spatial reorganization of the cytoskeleton,leading to different local forces which mediate nucleus alteration such as orientation,morphology,expression of Lamin A/C and chromatin condensation.Specifically,in the triangular prism and cuboid micropatterns,the ordered F-actin fibers are distributed over and fully transmit compressive forces to the nucleus,which results in nuclear flattening and stretching of nuclear pores,thus enhancing the nuclear import of YES-associated protein(YAP).Furthermore,the activation of YAP significantly enhances the paracrine of MSCs and upregulates the secretion of angiogenic growth factors.In contrast,the fewer compressive forces on the nucleus in cylinder and cube micropatterns cause less YAP entering the nucleus.The skin repair experiment provides the first in vivo evidence that enhanced MSCs paracrine by 3D geometry significantly promotes tissue regeneration.The current study contributes to understanding the in-depth mechanisms of mechanical signals affecting cell function and provides inspiration for innovative design of biomaterials.

关 键 词：bioactive materials tissue regeneration 3D micropattern force PARACRINE MECHANOTRANSDUCTION 

分 类 号：Q25[生物学—细胞生物学]