Snake venom-defined fibrin architecture dictates fibroblast survival and differentiation

Zhao Wang, Jan Lauko, Amanda W. Kijas, Elliot P. Gilbert, Petri Turunen, Ramanathan Yegappan, Dongxiu Zou, Jitendra Mata and Alan E. Rowan ()
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Zhao Wang: The University of Queensland
Jan Lauko: The University of Queensland
Amanda W. Kijas: The University of Queensland
Elliot P. Gilbert: The University of Queensland
Petri Turunen: Institute of Molecular Biology
Ramanathan Yegappan: The University of Queensland
Dongxiu Zou: The University of Queensland
Jitendra Mata: Australian Nuclear Science and Technology Organisation
Alan E. Rowan: The University of Queensland

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Fibrin is the provisional matrix formed after injury, setting the trajectory for the subsequent stages of wound healing. It is commonly used as a wound sealant and a natural hydrogel for three-dimensional (3D) biophysical studies. However, the traditional thrombin-driven fibrin systems are poorly controlled. Therefore, the precise roles of fibrin’s biophysical properties on fibroblast functions, which underlie healing outcomes, are unknown. Here, we establish a snake venom-controlled fibrin system with precisely and independently tuned architectural and mechanical properties. Employing this defined system, we show that fibrin architecture influences fibroblast survival, spreading phenotype, and differentiation. A fine fibrin architecture is a key prerequisite for fibroblast differentiation, while a coarse architecture induces cell loss and disengages fibroblast’s sensitivity towards TGF-β1. Our results demonstrate that snake venom-controlled fibrin can precisely control fibroblast differentiation. Applying these biophysical principles to fibrin sealants has translational significance in regenerative medicine and tissue engineering.

Date: 2023
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DOI: 10.1038/s41467-023-36437-9

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