A mechanical-biochemical feedback loop regulates remodeling in the actin cytoskeleton

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Cytoskeletal actin assemblies transmit mechanical stresses, which are converted into biochemical signals.
• The interplay between mechanical and biochemical signaling in orchestrating complex cytoskeletal remodeling remains unclear.

Purpose of the Study:

• To investigate the cooperative mechanisms of mechanical and biochemical signaling in the remodeling of contractile actomyosin stress fibers.
• To elucidate how these signals synchronize actin disassembly and fiber contraction.

Main Methods:

• Studied spontaneous fracture and remodeling of actomyosin stress fibers.
• Developed and utilized a mathematical model to explain observed remodeling kinetics.
• Measured actin overlap in resting stress fibers.

Main Results:

• Fractured fibers showed synchronous recoil and accelerated actin disassembly, dependent on actin density and myosin II-driven contraction.
• A mathematical model revealed a feedback mechanism where increased actin filament overlap, above a threshold, triggers accelerated disassembly.
• This feedback, coupled with stress transmission, synchronizes disassembly and contraction, and accurately predicts remodeling kinetics in intact and resting fibers.

Conclusions:

• Coordinated mechanical and biochemical signaling enables actomyosin stress fibers to dynamically adapt to mechanical stresses.
• A feedback loop involving actin filament overlap and associated stresses regulates cytoskeletal remodeling.
• This mechanism allows extended actomyosin assemblies to self-regulate their structure and function in response to mechanical cues.