Matrix Stiffness-Driven FAK Splicing Tunes Cell Mechanosensing

    July 2026 in “ bioRxiv (Cold Spring Harbor Laboratory) ”
    Martial Millet, Juliette Gouhier, Olivier Chancy, Elise Tahon, William David Zakzuk Vivas, Émilie Pic, Gabriel Khelifi, Solange Landreville, Samer M. I. Hussein, Dwayne G. Stupack, François Bordeleau
    TLDR FAKΔe4 helps cells sense and respond to different stiffness levels in their environment.
    The study investigates how extracellular matrix (ECM) stiffness affects cell mechanosensing through focal adhesion kinase (FAK). Researchers identified a new FAK isoform, FAKΔe4, which lacks exon 4 and is regulated by substrate stiffness in a biphasic manner. This isoform influences optimal migration speed, invasion, focal adhesion dynamics, and YAP nuclear translocation at lower stiffness levels compared to the canonical FAK. The expression ratio of FAKΔe4 to canonical FAK determines the stiffness at which cells converge during durotaxis. These findings highlight FAKΔe4 as a crucial mechanosensing switch, enhancing our understanding of mechanotransduction.
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