Interplay between cytoskeletal stresses and cell adaptation under chronic flow

Area of Science:

• Cellular mechanics
• Biophysics
• Cytoskeletal dynamics

Background:

• Cells respond to mechanical forces like shear stress.
• The actin cytoskeleton and associated proteins like α-actinin are crucial for cellular structure and force transmission.
• Mechanosensitive ion channels (MSCs) are involved in cellular mechanotransduction.

Purpose of the Study:

• To investigate the dynamic changes in cytoskeletal stress and actin reorganization under chronic shear stress.
• To elucidate the role of mechanosensitive ion channels (MSCs) in cellular adaptation to shear stress.

Main Methods:

• Utilized stress-sensitive Förster Resonance Energy Transfer (FRET) sensors to measure cytoskeletal stresses in α-actinin.
• Applied chronic shear stress to cells and monitored actin cytoskeleton reorganization.
• Inhibited mechanosensitive ion channels (MSCs) using Gadolinium (Gd3+) and GsMTx4 to assess their involvement.

Main Results:

• Long-term shear stress reversibly reduced average α-actinin stress.
• Flow-induced cytoskeletal stress changes exhibited a dynamic three-phase response (decrease, increase, longer-term decrease).
• Actin cytoskeleton reorganized from parallel F-actin bundles to peripheral bundles.
• Inhibition of MSCs abolished shear stress-induced changes in cytoskeletal stress and actin reorganization.

Conclusions:

• Chronic shear stress induces dynamic changes in cellular mechanical properties and cytoskeletal organization.
• Calcium-permeable mechanosensitive ion channels (MSCs) are critical mediators of cellular adaptation to shear stress.
• This study highlights the role of MSCs in shear stress-induced cell adaptation.