Biology subjects

Lachina, V.

Publications and source records attributed to Lachina, V..

2 recordsLinked to original sources

bioRxiv2026

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 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.

biophysics↗

bioRxiv2025

Topological Analysis of the Human Lymph Node Reticular Network Predicts Outcome in Breast Cancer

Axillary lymph nodes (ALN) initiate local immune responses in breast cancer (BC) but how and when ALN become dysfunctional, facilitating metastasis, is unclear. We use unbiased computational approaches to quantify features of ALN stromal architecture. We identify PDGFR{beta} as a robust, immunomarker for human fibroblastic reticular cells (FRC) and use it to quantify how FRC network topology changes during BC progression and after treatment. ALN (n = 331) from 179 BC patients and 23 benign reactive controls were assessed for FRC network metrics, including lacunarity and branchpoints, alongside de-identified clinico-pathological data. We find in node-negative, triple-negative BC, neoadjuvant treatment induced denser FRC networks which correlated with improved survival. Conversely, denser FRC networks in node-positive patients correlated with worsened survival, regardless of BC subtype or treatment. Further, increased FRC alignment within metastases improved survival. We show that FRC network topology predicts prognosis in BC, providing a new avenue for mechanistic, translational research.

pathology↗