Theoretical model of membrane protrusions driven by curved active proteins

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Eukaryotic cells dynamically alter shape via membrane composition and cytoskeleton remodeling.
• Curved membrane protein complexes play a role in recruiting cytoskeletal forces.

Purpose of the Study:

• To extend a minimal physical model of a vesicle with mobile curved membrane proteins.
• To explore the model's capacity to generate filopodia-like protrusions.
• To investigate cell shape dynamics including endocytosis and macropinocytosis.

Main Methods:

• Simulations of a minimal physical model of a closed vesicle.
• Analysis of phase diagrams based on active forces, protein interactions, and spontaneous curvature.
• Modeling cytoskeletal forces from actin polymerization and altered force models for bundled structures.

Main Results:

• The model successfully predicts lamellipodia-like flat protrusions.
• New regimes were identified for the formation of filopodia-like tubular protrusions.
• Simulations with convex and concave protein components revealed ruffled clusters and invaginations resembling endocytosis and macropinocytosis.
• Altering the cytoskeleton force model to bundled structures resulted in filopodia-like shapes.

Conclusions:

• The extended physical model provides a framework for understanding diverse eukaryotic cell shape dynamics.
• The model can recapitulate the formation of both flat and tubular cellular protrusions.
• The findings offer insights into the biophysical mechanisms underlying cell motility and membrane trafficking processes.