Thermodynamic Driving Forces for Divalent Cations Binding to Zwitterionic Phospholipid Membranes

Area of Science:

• Biophysics
• Computational Chemistry
• Membrane Biophysics

Background:

• Phospholipid bilayers are crucial cell membrane components.
• Ion interactions with membranes influence cellular processes.
• Understanding divalent cation binding is key to membrane function.

Purpose of the Study:

• To calculate free energies of Ca2+, Mg2+, and Zn2+ binding to zwitterionic phospholipid bilayers.
• To investigate the entropic and enthalpic contributions to ion-membrane binding.
• To elucidate the role of hydration and dehydration in ion binding affinity.

Main Methods:

• Molecular dynamics (MD) simulations.
• Enhanced umbrella sampling (EUS) technique.
• Free energy decomposition into entropic and enthalpic components.

Main Results:

• Ca2+ exhibits the highest binding affinity, with an overall endothermic binding process.
• Ca2+ dehydration is favorable, allowing coordination with lipids and increased entropy.
• High Ca2+ concentrations create electrostatic barriers, reducing entropy; Mg2+ and Zn2+ binding is exothermic and less favorable due to hydration.

Conclusions:

• Divalent cation binding to phospholipid bilayers is complex, influenced by hydration/dehydration.
• Ca2+ binding is entropically driven and can be modulated by ion concentration.
• Differential ion hydration states explain the varying binding affinities of Ca2+, Mg2+, and Zn2+.