Mechanical properties of anionic asymmetric bilayers from atomistic simulations

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Mechanotransduction relies on cell membrane deformation to activate mechanosensitive (MS) proteins.
• Anionic lipids are known to influence protein function, but their effect on membrane mechanics is less understood.
• Predicting lipid bilayer deformation under mechanical stress is key to understanding mechanotransduction.

Purpose of the Study:

• To investigate how anionic lipids (phosphatidylserine and PIP2) modulate the mechanical properties of lipid bilayers.
• To test the hypothesis that anionic lipids indirectly affect MS proteins by altering bilayer mechanics.
• To provide insights into the role of membrane mechanics in mechanosensitive protein function.

Main Methods:

• All-atom molecular dynamics simulations were employed to compute bilayer mechanical properties.
• Key properties calculated include bending rigidity (KC), area compressibility (KA), and surface shear viscosity (ηm).
• Simulations were performed on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PC) bilayers with and without anionic lipids (PS, PIP2) and cholesterol.

Main Results:

• Phosphatidylinositol bisphosphate (PIP2) at 20% in the lower leaflet had minimal impact on PC bilayer mechanical properties.
• Phosphatidylserine (PS) reduced bilayer bending rigidity by 22%.
• Cholesterol significantly increased all three mechanical constants (KC, KA, ηm) in PIP2-enriched membranes.

Conclusions:

• Anionic lipids, particularly PS, can significantly alter lipid bilayer mechanical properties, impacting membrane tension and curvature.
• The reduction in bending rigidity by PS suggests a mechanism for indirect modulation of MS protein activity.
• These findings have implications for understanding mechanotransduction, especially concerning MS piezo channels.