Cellular elasticity drives mechano-adaptation against fluid shear stress.

Area of Science:

• Cell Biology
• Biophysics
• Cancer Research

Background:

• Cancer cells exhibit adaptability to external biophysical cues.
• The role of cytoskeletal remodeling in cancer cell mechano-adaptation remains underexplored.

Purpose of the Study:

• To investigate how non-muscle myosin II (NMII) activity and self-organization contribute to cancer cell mechano-adaptation under fluid shear stress (FSS).

Main Methods:

• Studied NMII activity, actin filament reorganization, and cellular elastic properties in cancer cells exposed to FSS.
• Utilized small interfering RNA, (-)blebbistatin, and Y27632 to inhibit NMII.
• Assessed cyto-nuclear coupling, nuclear import of YAP1/TAZ, and gene expression changes.

Main Results:

• NMII activity and self-organization regulate cancer cell elastic properties under FSS.
• NMII forms aligned stacks with actin filaments, enabling cellular stretching.
• NMII inhibition disrupts stack formation and cellular elasticity.
• NMII-mediated elasticity influences cyto-nuclear coupling via nesprin2, affecting YAP1/TAZ nuclear import.

Conclusions:

• NMII-driven cellular elasticity is a key mechanism for cancer cell mechano-adaptation to FSS.
• This process impacts mechanoresponsive pathways, influencing gene expression to decrease cancer cell growth and migration.