Three-dimensional morphodynamic simulations of macropinocytic cups.

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Macropinocytosis is a vital cellular process for non-specific fluid uptake.
• The mechanism of initial cup formation in macropinocytosis, unlike phagocytosis, is not well understood.
• Understanding this process is key to cell growth, immune surveillance, and viral entry.

Purpose of the Study:

• To computationally model the formation of macropinocytosis cups.
• To investigate the biophysical mechanisms driving self-enclosing membrane structures.
• To identify key factors regulating efficient macropinocytosis.

Main Methods:

• Developed a computational framework coupling reaction-diffusion signaling with membrane deformation.
• Simulated the interplay between active signaling patches and plasma membrane dynamics.
• Analyzed the influence of patch size, protrusive force, and cortical tension.

Main Results:

• Demonstrated that localized protrusive force at signaling patch edges drives self-enclosing cup formation.
• Showed that efficient uptake depends on balancing patch size, protrusive force, and cortical tension.
• Observed emergent behaviors like cyclic cup formation, multiple cups, and cup-splitting.

Conclusions:

• Macropinocytosis cup formation is a self-organized process driven by reaction-diffusion and membrane mechanics.
• The model provides a unified mechanism for various macropinocytosis cup morphologies.
• This work elucidates fundamental biophysical principles governing cellular membrane dynamics.