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Actin polymerization kinetics, cap structure, and fluctuations.

Dimitrios Vavylonis1, Qingbo Yang, Ben O'Shaughnessy

  • 1Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 9, 2005
PubMed
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This study models actin filament polymerization kinetics, revealing that filament growth rates depend on ATP-actin and ADP-P(i)-actin cap dynamics. Fluctuations in filament length are linked to these caps and may explain observed experimental variations.

Area of Science:

  • Biophysics
  • Cell Biology
  • Biochemistry

Background:

  • Actin polymerization into dynamic structures is vital for eukaryotic cell function.
  • In vitro experiments often measure individual actin filament polymerization kinetics.
  • Understanding these kinetics is crucial for cell motility and structure.

Purpose of the Study:

  • To model actin filament polymerization kinetics, incorporating polymerization, depolymerization, ATP hydrolysis, and phosphate release.
  • To relate filament growth rates to the dynamics of ATP-actin and ADP-P(i)-actin caps.
  • To investigate the origin of observed large length fluctuations in actin filaments near the critical concentration.

Main Methods:

  • Developed a kinetic model for actin polymerization.

Related Experiment Videos

  • Accounted for monomer addition, removal, ATP hydrolysis, and phosphate release.
  • Analyzed the structure and dynamics of ATP-actin and ADP-P(i)-actin caps at filament ends.
  • Described filament length fluctuations using the length diffusion coefficient (D).

    • Main Results:

    • Identified a short ATP cap and a long ADP-P(i) cap at the critical concentration (c(crit)) of the barbed end.
    • Demonstrated a strong relationship between growth rates, c(crit), and cap structure/dynamics.
    • Found that the length diffusion coefficient (D) peaks below c(crit) due to alternating capped/uncapped states.
    • Observed that fluctuations above c(crit) are enhanced but smaller than experimentally reported values.

    Conclusions:

    • The model provides insights into actin filament growth dynamics and the role of caps.
    • The predicted length fluctuations differ from some experimental observations, suggesting potential alternative growth mechanisms.
    • Further measurements of D are recommended to elucidate the source of experimental length fluctuations.