journal article·2023-12Open access

Programmable and Reversible Integrin‐Mediated Cell Adhesion Reveals Hysteresis in Actin Kinetics that Alters Subsequent Mechanotransduction

Zheng Zhang, Hongyuan Zhu, Guoqing Zhao, Yunyi Miao, Lingzhu Zhao, Jinteng Feng, Huan Zhang, Run Miao, Lin Sun, Bin Gao, Wencheng Zhang, Zheng Wang, Jianfang Zhang, Ying Zhang, Hui Guo, Feng Xu, Tian Jian Lu, Guy M. Genin, Min Lin

Advanced Science· Volume 10· Issue 35

Abstract

Abstract Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time‐varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA‐driven molecular system is developed wherein the integrin‐binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F‐actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with the result that hysteresis can completely change how hMSCs transduce ECM stiffness. Results are dramatically different from well‐known results for mechanotransduction on static substrates, but are consistent with a mathematical model of F‐actin fragments retaining structure following loss of integrin ligation and participating in subsequent repolymerization. These findings suggest that cyclic integrin‐mediated adhesion alters the mechanosensing of ECM stiffness by hMSCs through transient, hysteretic memory that is stored in F‐actin.
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Research context

OpenAlex topics: Cellular Mechanics and Interactions · Hippo pathway signaling and YAP/TAZ · Cell Adhesion Molecules Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University Xi'an 710049 P. R. China

Bioinspired Engineering and Biomechanics Center (BEBC) Xi'an Jiaotong University Xi'an 710049 P. R. China

Department of Medical Oncology First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 P. R. China

Department of Endocrinology Second Affiliated Hospital of Air Force Military Medical University Xi'an 710038 P. R. China

Department of Hepatobiliary Surgery First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 P. R. China

Department of Gynaecology and Obstetrics of Xijing Hospital, Fourth Military Medical University 710054 Xi'an P. R. China

Xijing 986 Hospital Department Fourth Military Medical University Xi'an 710054 P. R. China

State Key Laboratory of Mechanics and Control of Mechanical Structures Nanjing University of Aeronautics and Astronautics Nanjing 210016 P. R. China

Department of Mechanical Engineering & Materials Science Washington University in St. Louis St. Louis MO 63130 USA

NSF Science and Technology Center for Engineering Mechanobiology Washington University in St. Louis St. Louis MO 63130 USA

Funding

National Natural Science Foundation of China · China Postdoctoral Science Foundation

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