Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics

Boguang Yang, Kongchang Wei, Claudia Loebel, Kunyu Zhang, Qian Feng, Rui Li, Siu Hong Dexter Wong, Xiayi Xu, Chunhon Lau, Xiaoyu Chen, Pengchao Zhao, Chao Yin, Jason A. Burdick, Yi Wang () and Liming Bian ()
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Boguang Yang: The Chinese University of Hong Kong
Kongchang Wei: The Chinese University of Hong Kong
Claudia Loebel: University of Pennsylvania
Kunyu Zhang: The Chinese University of Hong Kong
Qian Feng: The Chinese University of Hong Kong
Rui Li: The Chinese University of Hong Kong
Siu Hong Dexter Wong: The Chinese University of Hong Kong
Xiayi Xu: The Chinese University of Hong Kong
Chunhon Lau: The Chinese University of Hong Kong
Xiaoyu Chen: The Chinese University of Hong Kong
Pengchao Zhao: The Chinese University of Hong Kong
Chao Yin: The Chinese University of Hong Kong
Jason A. Burdick: University of Pennsylvania
Yi Wang: The Chinese University of Hong Kong
Liming Bian: The Chinese University of Hong Kong

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23120-0

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