Affiliation:
1. The Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University Xi'an 710004 P. R. China
2. 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
3. Bioinspired Engineering and Biomechanics Center (BEBC) Xi'an Jiaotong University Xi'an 710049 P. R. China
4. Department of Physics Virginia Polytechnic Institute and State University Blacksburg Virginia 24061 United States
5. Center for Soft Matter and Biological Physics Virginia Polytechnic Institute and State University Blacksburg Virginia 24061 United States
Abstract
AbstractSoft‐hard tissue interfaces are widespread in the human body, where matrix stiffness gradient at the cellular scale is a typical biophysical cue that cells experience. However, most studies have focused on the large‐scale matrix stiffness gradient that affected cell fate. It is still necessary to elucidate the impact of cellular‐scale matrix stiffness gradient on cell behavior and function, such as mesenchymal stem cell (MSC) immunoregulation. In this study, it is observed that stiffness gradient strength (SGS) at a typical soft‐hard tissue interface (e.g., periodontal ligament (PDL)‐alveolar bone (AB) enthesis) in periodontitis is lower than that in health, due to low mineral content gradient there. Meanwhile, MSCs residing at PDL‐AB enthesis in periodontitis show an anti‐inflammatory phenotype (i.e., MSC2). To investigate how the stiffness gradient affects the MSC immunoregulation, both high and low SGS in vitro is recapitulated. Combined with mathematical modeling, low SGS minimizes the ability of cell polarization in guiding the MSC2, which is probably driven by the reduced polarization of integrin β1 clusters and myosin IIB, leading to H4K16ac localization‐dependent chromatin opening that facilitates TLR3 gene expression. This study establishes the molecular mechanisms by which MSCs respond to cellular‐scale stiffness gradient at PDL‐AB enthesis for regulating the immunophenotype development.
Funder
Fundamental Research Funds for the Central Universities
National Natural Science Foundation of China
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials