Fibronectin Extra Domains tune cellular responses and confer topographically distinct features to fibril networks

ABSTRACT Cellular fibronectin (FN; also known as FN1) variants harboring one or two alternatively spliced so-called extra domains (EDB and EDA) play a central bioregulatory role during development, repair processes fibrosis. Yet, how the impact fibrillar assembly function of molecule remains unclear. Leveraging unique biological toolset image analysis pipeline for direct comparison variants, we demonstrate that presence both impacts FN assembly, physical properties matrix. When presented to FN-null fibroblasts, domain-containing differentially regulate pH homeostasis, survival TGF-? signaling by tuning magnitude cellular responses, rather than triggering independent molecular switches. Numerical analyses fiber topologies highlight significant differences in variant-specific structural features provide first step development generative model networks unravel mechanisms investigate functional versatility extracellular matrix landscapes. This article has an associated First Person interview with author paper.