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Title: Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics
Authors: Yang, B
Wei, K
Loebel, C
Zhang, K
Feng, Q
Li, R
Wong, SHD 
Xu, X
Lau, C
Chen, X
Zhao, P
Yin, C
Burdick, JA
Wang, Y
Bian, L
Issue Date: 2021
Source: Nature communications, 2021, v. 12, 3514
Abstract: 3D culture of cells in designer biomaterial matrices provides a biomimetic cellular microenvironment and can yield critical insights into cellular behaviours not available from conventional 2D cultures. Hydrogels with dynamic properties, achieved by incorporating either degradable structural components or reversible dynamic crosslinks, enable efficient cell adaptation of the matrix and support associated cellular functions. Herein we demonstrate that given similar equilibrium binding constants, hydrogels containing dynamic crosslinks with a large dissociation rate constant enable cell force-induced network reorganization, which results in rapid stellate spreading, assembly, mechanosensing, and differentiation of encapsulated stem cells when compared to similar hydrogels containing dynamic crosslinks with a low dissociation rate constant. Furthermore, the static and precise conjugation of cell adhesive ligands to the hydrogel subnetwork connected by such fast-dissociating crosslinks is also required for ultra-rapid stellate spreading (within 18 h post-encapsulation) and enhanced mechanosensing of stem cells in 3D. This work reveals the correlation between microscopic cell behaviours and the molecular level binding kinetics in hydrogel networks. Our findings provide valuable guidance to the design and evaluation of supramolecular biomaterials with cell-adaptable properties for studying cells in 3D cultures.
Publisher: Nature Publishing Group
Journal: Nature communications 
EISSN: 2041-1723
DOI: 10.1038/s41467-021-23120-0
Rights: © The Author(s) 2021
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit licenses/by/4.0/.
The following publication Yang, B., Wei, K., Loebel, C. et al. Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics. Nat Commun 12, 3514 (2021) is available at
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