Predicting protein curvature sensing across membrane compositions with a bilayer continuum model

Area of Science:

• Biophysics
• Cell Biology
• Materials Science

Background:

• Cytoplasmic proteins require membrane recruitment for cellular functions like endocytosis and cell division.
• Many proteins exhibit 'curvature sensing,' binding preferentially to highly curved membrane surfaces.
• Previous studies faced challenges in systematically characterizing lipid composition's effect on curvature sensing due to simultaneous changes in membrane properties.

Purpose of the Study:

• To develop and apply a bilayer continuum membrane model to systematically quantify the impact of lipid composition on protein curvature sensing.
• To evaluate both energetic and structural changes in vesicles upon protein insertion.
• To provide a predictive tool for understanding protein-membrane interactions.

Main Methods:

• Development of a bilayer continuum membrane model using continuous triangular meshes for monolayers.
• Introduction of a coupling energy term accounting for membrane incompressibility and lipid tilt energetics.
• Validation of the model against in vitro experiments and all-atom molecular dynamics (MD) simulations.

Main Results:

• The model accurately predicts stronger curvature sensing in membranes with distinct lipid tail groups (e.g., POPC vs. DOPC vs. DLPC).
• Membrane thickness and lipid shape (wedge shape) were identified as primary drivers for variations in curvature sensing, not head-group chemistry.
• Asymmetry in lipid composition between membrane leaflets showed a negligible effect on membrane mechanics after protein insertion.

Conclusions:

• The developed multi-scale membrane model effectively quantifies how changes in membrane material properties influence protein curvature sensing.
• This approach enables efficient prediction of how membrane composition affects protein-membrane energetics across various curvatures.
• Understanding these mechanisms is crucial for predicting how proteins target specific membranes at the right time and place.