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Journal Articles Journal of Cell Science Year : 2021

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

Laurent Counillon
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  • PersonId : 1069508
Xavier Descombes
Laure Blanc-Féraud
Ellen van Obberghen-Schilling
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  • PersonId : 853772

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 and fibrosis. Yet, how the extra domains impact fibrillar assembly and function of the molecule remains unclear. Leveraging a unique biological toolset and image analysis pipeline for direct comparison of the variants, we demonstrate that the presence of one or both extra domains impacts FN assembly, function and physical properties of the matrix. When presented to FN-null fibroblasts, extra domain-containing variants differentially regulate pH homeostasis, survival, and TGF- β by tuning the magnitude of cellular responses, rather than triggering independent molecular switches. Numerical analyses of fiber topologies highlight significant differences in variant-specific structural features and provide a first step for the development of a generative model of FN networks to unravel assembly mechanisms and investigate the physical and functional versatility of extracellular matrix landscapes.
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Dates and versions

hal-03282792 , version 1 (09-07-2021)

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Georgios Efthymiou, Agata Radwanska, Anca-Ioana Grapa, Stéphanie Beghelli-de La Forest Divonne, Dominique Grall, et al.. Fibronectin Extra Domains tune cellular responses and confer topographically distinct features to fibril networks. Journal of Cell Science, 2021, ⟨10.1242/jcs.252957⟩. ⟨hal-03282792⟩
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