The extracellular matrix regulates tissue mechanics to enable cyclic lymph node remodelling and sustained immunity

Tissue shape and function are defined by the mechanical interactions of cellular and extracellular components. Lymph nodes cyclically remodel in response to immune challenges whilst preserving essential stromal structures. However, the relative contributions of the fibroblastic reticular stromal cell network and the ensheathed extracellular matrix, remain undefined. We quantified the contribution of ECM to the viscoelastic properties of lymph nodes to parameterise an in silico model exploring the FRC network's adaptation to pressure-driven tissue expansion. The balance between tissue pressure, FRC contractility and ECM stiffness permit robust remodelling and growth, while maintaining physiological geometries and balancing force distribution. Local perturbation of ECM stiffness or FRC contractility disrupts force distribution globally and impacts FRC proliferation and tissue expansion. Spatially dispersed perturbations exert higher impact on tissue architecture than equivalent localised perturbations, with effects propagating across the network. The integration of cellular and extracellular mechanics thereby enables robust lymph node remodelling.