Nanoscale distribution of bioactive ligands on biomaterials regulates cell mechanosensing through translocation of actin into the nucleus

• 成果类型: Article
• 署名作者: Liu, Xiaojing; Zhang, Man; Wang, Peng; Zheng, Kaikai; Wang, Xinlei; Xie, Wenyan; Pan, Xiaokai; Shen, Runjia; Liu, Ruili; Ding, Jiandong; Wei, Qiang
• 署名单位: Fudan University; Sichuan University; Shandong University; Sichuan University; Harbin Institute of Technology; Sichuan University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11992
• DOI: 10.1073/pnas.2501264122
• 发表日期: 2025-03-05
• 关键词: extracellular-matrix; force transmission; adhesion; complex; yap; mechanotransduction; differentiation; ORGANIZATION; activation; mechanisms

摘要

Cells respond to adhesive ligands such as arginine- glycine- aspartate (RGD) through integrins, which regulates cellular activities via influencing cytoskeleton assembly. Herein, we report that the nanoscale distribution of active ligands on biomaterials regulates cells through not only cytoplasmic tension but also nuclear tension. This is particularly related to translocation of actin into nucleus and highlighted in our interpretation of an abnormal phenomenon that large RGD nanospacing (>70 nm) disassembles integrin clusters, inhibits cell adhesion, but promotes osteogenic differentiation of mesenchymal stem cells. Our studies reveal that the unstable adhesion at the 150 nm RGD distance The compartment polymerization of more G- actins to filamentous actins in nucleus increases nuclear tension, facilitating transcription activity and releasing calcium ions from the endoplasmic reticulum. This noncanonical mechanotransduction process sheds insight into mechanotransduction pertinent to cell-material interactions.