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bioRxiv · 10.64898/2025.11.28.691198

Mechanical cues of an interpenetrating polysaccharide matrix regulate self-assembly of collagen fibers

Tavakoli Joorabi, F.·Derr, N. J.·Li, Z.·Nerger, B. A.·Rycroft, C. H.·Mooney, D. J.·Vining, K. H.
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Abstract

Collagen molecules self-assemble into supramolecular fibers within a molecularly crowded, polysaccharide-rich extracellular matrix (ECM). The ECM typically has fluid-like, viscoelastic properties that can be quantified rheologically. Here, we determine that the viscoelasticity of a polysaccharide alginate ECM regulates the assembly of type I collagen fibers. The viscoelasticity and shear moduli of the alginate network were tuned by the polymer weight percentage and degree of cooperative ionic and covalent norbornene-tetrazine crosslinking. Stepwise shear strain applied to covalently-crosslinked hydrogels generated higher stress than in ionic hydrogels. Hydrogels with reduced viscoelasticity also showed a reduction in water permeability. Second-harmonic generation confocal imaging revealed that decreasing viscoelasticity significantly suppressed collagen fiber self-assembly. Simulations demonstrated a mechanical coupling of the hydrogel network and the aggregate size of collagen molecules. Increased covalent crosslinking impaired the rate and magnitude of self-assembly in simulations and experimental results. These results suggest that ECM viscoelasticity plays a role in modulating the assembly and structural organization of collagen within the matrix. More broadly, they provide a framework for understanding how ECM mechanical properties can influence the assembly and organization of fibrillar macromolecules.

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Tavakoli Joorabi, F., Derr, N. J., Li, Z., Nerger, B. A., Rycroft, C. H., Mooney, D. J., Vining, K. H.. 2025-12-02. Mechanical cues of an interpenetrating polysaccharide matrix regulate self-assembly of collagen fibers. https://doi.org/10.64898/2025.11.28.691198

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