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Disrupting Titin Mechanics with TEVs-TTN Uncovers Muscle Disease Mechanisms

The CNIC innovation lets researchers mimic titin mutations in muscle cells to study disease processes.

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Overview

  • The CNIC team led by Jorge Alegre-Cebollada published their TEVs-TTN study in Nature Biomedical Engineering on June 5, 2025.
  • TEVs-TTN enables precise mechanical dissection of titin by controlled cleavage of its force-bearing domains within muscle cells.
  • Researchers reproduced sarcomere disassembly and pathological features of TTN mutations, including fiber atrophy, nuclear internalization, and mitochondrial aggregation.
  • Muscle cells remained viable despite complete loss of sarcomere structure, revealing unexpected resilience pathways.
  • Funded by the European Research Council and EMBO, the tool addresses the lack of animal models and could be adapted to study other mechanically active proteins.