Stochastic model of clathrin-coated pit assembly

Area of Science:

• Cell biology
• Biophysics
• Molecular dynamics

Background:

• Fluorescence microscopy allows real-time observation of clathrin-coated pit (CCP) assembly dynamics.
• CCP assembly exhibits significant heterogeneity, with some pits being long-lived (productive) and others short-lived (abortive).
• Variance exists in CCP lifetimes within both productive and abortive populations.

Purpose of the Study:

• To develop a stochastic biophysical model explaining CCP assembly heterogeneity.
• To link CCP energetics and assembly kinetics to observed dynamics.
• To elucidate the role of cargo binding in CCP stabilization and growth.

Main Methods:

• Stochastic biophysical modeling of clathrin-coated pit assembly.
• Analysis of CCP energetics and assembly kinetics.
• Comparison of model predictions with experimental data on CCP lifetimes.

Main Results:

• Without cargo, CCP assembly faces a high energy barrier, leading to predominantly abortive pits.
• Cargo binding stabilizes CCPs, facilitating their growth towards vesicle formation.
• Model-predicted lifetime distributions for abortive pits align with experimental observations.
• The stochastic nature of assembly significantly contributes to the wide lifetime distribution of productive CCPs.

Conclusions:

• A stochastic biophysical model successfully explains the heterogeneous dynamics of clathrin-coated pit assembly.
• Cargo binding is crucial for stabilizing CCPs and enabling productive vesicle formation.
• The inherent stochasticity in the assembly process is a key factor in the observed variance of productive CCP lifetimes.