Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties

Area of Science:

• Cell Biology
• Biophysics
• Developmental Biology

Background:

• Tissue spreading requires cells to deform while maintaining integrity.
• The mechanisms balancing flexibility and mechanical resilience in spreading tissues are not fully understood.

Purpose of the Study:

• To investigate the role of keratin intermediate filaments in regulating tissue mechanics during epithelial spreading.
• To elucidate how keratin networks adapt to mechanical stress during embryonic development.

Main Methods:

• In vivo imaging of zebrafish embryonic development (EVL spreading over yolk cell).
• Genetic manipulation to interfere with keratin function.
• Tissue rheology measurements.
• Computational modeling using a vertex model with mechanochemical feedback.

Main Results:

• Keratin network maturation in the enveloping cell layer (EVL) is stress-induced during tissue spreading.
• Stress-induced keratin maturation increases EVL tissue viscosity, preventing rupture.
• Keratins in the yolk cell are essential for mechanosensitive actomyosin network contraction and force generation.
• Keratins play dual roles in force production and tissue resilience.

Conclusions:

• Keratin intermediate filaments are crucial for adapting tissue mechanical resilience to spreading-induced stresses.
• Keratins ensure uniform and robust tissue spreading by balancing force generation and cellular integrity.
• This study reveals a mechanosensitive role for keratins in coordinating tissue-level morphogenesis.