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

摘要: The mechanical environment plays an important role in cell signaling and tissue homeostasis. Unraveling connections between externally applied loads the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for examining fine details of behavior, but they require validation at multiple scales. In this study, we developed model that captured anisotropy heterogeneity cell-compacted collagen gel subjected to off-axis hold test subsequently biaxial extension. both experiments, ECM reorganized nonaffine heterogeneous manner depended on interactions fiber networks. Simulations predicted tensile compressive forces were produced accommodate macroscopic displacements. Fiber simulation ranged from −11.3 437.7 nN, with significant fraction fibers under compression (12.1% during stretch). network restructuring serves as example how modeling techniques theoretical framework understanding relationships structure tissue-level properties microscopic rearrangements could lead mechanotransductive signaling.