Monitoring the poroelastic response of collagen gels with embedded senescent fibroblasts reveals tissue softening associated with collagen network reorganization

Cacheux, J.; Quenan, T.; Alcaide, D.; Ordonez-Miranda, J.; Jalabert, L.; Nakano, S.; Nakanishi, M.; Cordelier, P.; Bancaud, A.; Matsunaga, Y. T.

doi:10.1101/2025.04.18.649513

bioRxiv · 10.1101/2025.04.18.649513

Monitoring the poroelastic response of collagen gels with embedded senescent fibroblasts reveals tissue softening associated with collagen network reorganization

Cacheux, J.·Quenan, T.·Alcaide, D.·Ordonez-Miranda, J.·Jalabert, L.·Nakano, S.·Nakanishi, M.·Cordelier, P.·Bancaud, A.·Matsunaga, Y. T.

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Abstract

The poroelastic properties of tissues regulate molecular transport and mechanical signaling, yet their evolution during aging remains poorly understood. In particular, senescent fibroblasts accumulate in aged tissues, contributing to extracellular matrix (ECM) remodeling, but their impact on tissue mechanics and permeability is unclear. In this study, we developed a microfluidic-based in vitro model to assess the poroelastic properties of collagen gels embedded with senescent fibroblasts over time. Our approach integrates periodic pressure actuation with real-time pressure monitoring in a sealed air cavity, enabling the detection of fluid permeation and solid matrix deformations. We analyze our data using analytical and numerical models based on a porohyperelastic framework. This framework combines compressible Neo-Hookean elasticity with the Kozeny-Carman permeability relationship. We demonstrate that senescent fibroblasts induce a progressive softening of the ECM without altering its permeability. Immunostaining reveals that this softening correlates with structural reorganization of the collagen network, characterized by increased branching and network remodeling. Our findings provide insights into the biomechanical effects of senescent fibroblasts on ECM homeostasis. We further argue that our platform offers a unique solution to investigate ECM remodeling not only in aging but also fibrosis, cancer progression, or regenerative medicine strategies.

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Cacheux, J., Quenan, T., Alcaide, D., Ordonez-Miranda, J., Jalabert, L., Nakano, S., Nakanishi, M., Cordelier, P., Bancaud, A., Matsunaga, Y. T.. 2025-04-23. Monitoring the poroelastic response of collagen gels with embedded senescent fibroblasts reveals tissue softening associated with collagen network reorganization. https://doi.org/10.1101/2025.04.18.649513

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