The Extracellular Matrix Regulates Tissue Mechanics to Enable Cyclic Lymph Node Remodelling for 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 tissue architecture, comprised of a stromal fibroblastic reticular cell (FRC) network and extracellular matrix (ECM) it ensheaths. We experimentally quantified the contribution of ECM to the viscoelastic properties of the FRC network to parameterise an in silico model exploring factors affecting the FRC network's adaptation to lymph node expansion. The balance between tissue pressure, FRC contractility, and ECM stiffness permit robust tissue remodelling, while maintaining physiological geometries. Local perturbation of ECM stiffness or FRC contractility disrupts force distribution and impacts FRC proliferation and tissue expansion. Spatially dispersed perturbations exert higher impact on tissue remodelling than equivalent localised perturbations, with effects propagating across the network. The lymph node provides a system for studying the integration of cellular and extracellular mechanics during dramatic tissue remodelling.