Reversible Host-Guest Crosslinks in Supramolecular Hydrogels for On-Demand Mechanical Stimulation of Human Mesenchymal Stem Cells.

Autor: Linke P; Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, 69120, Heidelberg, Germany., Munding N; Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, 69120, Heidelberg, Germany., Kimmle E; Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, 69120, Heidelberg, Germany., Kaufmann S; Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, 69120, Heidelberg, Germany., Hayashi K; Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, 606-8501, Japan., Nakahata M; Department of Macromolecular Science, Graduate School of Science, Osaka University, Osaka, 560-0043, Japan., Takashima Y; Department of Macromolecular Science, Graduate School of Science, Osaka University, Osaka, 560-0043, Japan., Sano M; Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China., Bastmeyer M; Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, 606-8501, Japan.; Cell and Neurobiology, Zoological Institute, Karlsruhe Institute of Technology, 76131, Karlsruhe, Germany.; Institute for Biological and Chemical Systems - Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology, 76334, Eggenstein-Leopoldshafen, Germany., Holstein T; Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, 606-8501, Japan.; Molecular Genetics and Evolution, Centre for Organismal Studies, Heidelberg University, 69221, Heidelberg, Germany., Dietrich S; Department of Internal Medicine V, Hematology, Oncology, Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.; Department of Haematology, Oncology, and Clinical Immunology, Universitätsklinikum Düsseldorf, 40225, Düsseldorf, Germany., Müller-Tidow C; Department of Internal Medicine V, Hematology, Oncology, Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany., Harada A; The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047, Japan., Ho AD; Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, 606-8501, Japan.; Department of Internal Medicine V, Hematology, Oncology, Rheumatology, University Hospital Heidelberg, 69120, Heidelberg, Germany.; Molecular Medicine Partnership Unit Heidelberg, EMBL and Heidelberg University, 69120, Heidelberg, Germany., Tanaka M; Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, 69120, Heidelberg, Germany.; Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, 606-8501, Japan.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Apr; Vol. 13 (10), pp. e2302607. Date of Electronic Publication: 2023 Dec 25.
DOI: 10.1002/adhm.202302607
Abstrakt: Stem cells are regulated not only by biochemical signals but also by biophysical properties of extracellular matrix (ECM). The ECM is constantly monitored and remodeled because the fate of stem cells can be misdirected when the mechanical interaction between cells and ECM is imbalanced. A well-defined ECM model for bone marrow-derived human mesenchymal stem cells (hMSCs) based on supramolecular hydrogels containing reversible host-guest crosslinks is fabricated. The stiffness (Young's modulus E) of the hydrogels can be switched reversibly by altering the concentration of non-cytotoxic, free guest molecules dissolved in the culture medium. Fine-adjustment of substrate stiffness enables the authors to determine the critical stiffness level E* at which hMSCs turn the mechano-sensory machinery on or off. Next, the substrate stiffness across E* is switched and the dynamic adaptation characteristics such as morphology, traction force, and YAP/TAZ signaling of hMSCs are monitored. These data demonstrate the instantaneous switching of traction force, which is followed by YAP/TAZ signaling and morphological adaptation. Periodical switching of the substrate stiffness across E* proves that frequent applications of mechanical stimuli drastically suppress hMSC proliferation. Mechanical stimulation across E* level using dynamic hydrogels is a promising strategy for the on-demand control of hMSC transcription and proliferation.
(© 2023 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)
Databáze: MEDLINE