Nucleation causes an actin network to fragment into multiple high-density domains

Area of Science:

• Cellular biology
• Biophysics
• Computational biology

Background:

• Actin networks are essential for cell structure and function.
• Spontaneous actin filament nucleation is kinetically disfavored.
• Branching nucleation by actin-related protein (Arp2/3) is critical for actin self-organization.

Purpose of the Study:

• To investigate the impact of varying Arp2/3 concentrations on actin network dynamics.
• To understand how Arp2/3 concentration influences F-actin organization and domain formation.
• To explore the transition from coherent to fragmented actin cytoskeleton.

Main Methods:

• Simulated actin networks using the MEDYAN platform for 2000s.
• Varied Arp2/3 concentrations in biologically relevant reaction volumes (>20 µm³).
• Analyzed F-actin density fields and domain dynamics using drift-diffusion models.

Main Results:

• Increased Arp2/3 dynamics led to more short filaments and higher network treadmilling rates.
• Low Arp2/3 concentrations resulted in a single, contractile F-actin domain.
• Elevated Arp2/3 levels (≥10 nM) caused fragmentation into dynamic, merging/splitting domains.

Conclusions:

• Tuning Arp2/3 concentration controls actin network organization, from coherent to fragmented states.
• Fragmented actin domains can respond independently to local signals.
• The fragmented state is stochastically favored, with the network slowly drifting towards it.