Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels

The mechanical environment plays an important role in cell signaling and tissue homeostasis. Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for exami...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2009-10, Vol.106 (42), p.17675-17680
Hauptverfasser: Sander, Edward A, Stylianopoulos, Triantafyllos, Tranquillo, Robert T, Barocas, Victor H
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container_issue 42
container_start_page 17675
container_title Proceedings of the National Academy of Sciences - PNAS
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creator Sander, Edward A
Stylianopoulos, Triantafyllos
Tranquillo, Robert T
Barocas, Victor H
description The mechanical environment plays an important role in cell signaling and tissue homeostasis. Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for examining the fine details of tissue behavior, but they require validation at multiple scales. In this study, we developed a multiscale model that captured the anisotropy and heterogeneity of a cell-compacted collagen gel subjected to an off-axis hold mechanical test and subsequently to biaxial extension. In both the model and experiments, the ECM reorganized in a nonaffine and heterogeneous manner that depended on multiscale interactions between the fiber networks. Simulations predicted that tensile and compressive fiber forces were produced to accommodate macroscopic displacements. Fiber forces in the simulation ranged from -11.3 to 437.7 nN, with a significant fraction of fibers under compression (12.1% during off-axis stretch). The heterogeneous network restructuring predicted by the model serves as an example of how multiscale modeling techniques provide a theoretical framework for understanding relationships between ECM structure and tissue-level mechanical properties and how microscopic fiber rearrangements could lead to mechanotransductive cell signaling.
doi_str_mv 10.1073/pnas.0903716106
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subjects Anisotropy
Biochemistry
Biological Sciences
Biomechanical Phenomena
Cells
Collagen Type I - chemistry
Collagen Type I - physiology
Collagens
Compressive Strength - physiology
Connective tissues
Extracellular Matrix - chemistry
Extracellular Matrix - physiology
Fibroblasts
Fibroblasts - physiology
Fracture mechanics
Gels
Homeostasis - physiology
Humans
In Vitro Techniques
Mechanical engineering
Mechanics
Mechanotransduction, Cellular - physiology
Modeling
Models, Biological
Models, Molecular
Multiprotein Complexes
Multiscale modeling
Parametric models
Physical Sciences
Proteins
Signal Transduction - physiology
Tensile Strength - physiology
Tissues
title Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels
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