Liquid-like condensates mediate competition between actin branching and bundling

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Actin networks are crucial for cell motility, involving a balance between actin branching and bundling.
• Steric hindrance between branched actin filaments impedes bundling.
• Previously, protein condensates of either branching or bundling factors were shown to promote their respective functions.

Purpose of the Study:

• To investigate how simultaneous presence of branching and bundling proteins in a cellular environment affects actin network formation.
• To determine the factors governing whether a protein condensate promotes actin branching or bundling.

Main Methods:

• Addition of the branched actin nucleator, Arp2/3 complex, to condensates of the actin bundling protein, VASP.
• Observation of actin filament organization at varying actin to VASP ratios.
• Comparison with agent-based simulations.

Main Results:

• At low actin to VASP ratios, Arp2/3-mediated branching inhibited VASP-mediated bundling.
• At higher actin to VASP ratios, Arp2/3 addition resulted in aster-shaped structures with bundled filaments emerging from a branched core.
• These structures mimic cellular formations like filopodia emerging from lamellipodial networks.

Conclusions:

• Multi-component, liquid-like protein condensates can dynamically regulate the competition between actin branching and bundling.
• These condensates can organize higher-order actin structures relevant to cell morphology and motility.
• The findings provide insights into the mechanisms governing cytoskeletal organization in complex cellular environments.