F-actin architecture determines constraints on myosin thick filament motion

Area of Science:

• Cell Biology
• Biophysics
• Cytoskeletal Dynamics

Background:

• Active stresses within the cell cytoskeleton are crucial for cell functions like division and migration.
• While F-actin architecture's role in stress transmission is known, its impact on initial stress generation is less understood.

Purpose of the Study:

• To investigate how different F-actin network architectures influence the de novo generation of mechanical stresses.
• To elucidate the relationship between F-actin network geometry and the dynamics of myosin motors.

Main Methods:

• In vitro assembly of F-actin networks with varied architectures (branched vs. bundled) using Arp2/3 and formin mDia1 nucleation.
• Tracking embedded myosin thick filament motion within these networks.
• Correlating myosin dynamics with F-actin network deformation.

Main Results:

• Formin mDia1-nucleated networks (bundled) promote stress accumulation and actomyosin contractility.
• Arp2/3-nucleated networks (branched) inhibit stress accumulation by reducing myosin thick filament processivity.
• Myosin filament motion is constrained by local F-actin density and geometry, impacting stress generation.

Conclusions:

• F-actin network architecture plays a critical role in regulating the ab initio generation of cellular stresses.
• The geometry of F-actin networks dictates myosin motor activity and, consequently, stress accumulation and cell contractility.