Coarse-Grained Molecular Dynamics Simulations of Membrane-Trehalose Interactions

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• Trehalose (TRH) is known to stabilize biological membranes and affect lipid bilayer physical properties.
• Understanding trehalose-lipid interactions is crucial for comprehending membrane stabilization mechanisms.

Purpose of the Study:

• To investigate the interactions between trehalose (TRH) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid membranes using molecular dynamics (MD) simulations.
• To compare atomistic and coarse-grained (CG) simulation models for trehalose-lipid interactions.
• To analyze the effects of trehalose on membrane physical properties, including area per lipid, compressibility, and bending modulus.

Main Methods:

• Employed both atomistic and coarse-grained (CG) molecular dynamics (MD) simulations.
• Utilized modified Martini force-field models for CG simulations.
• Developed a two-site analytical model to describe sugar binding at the membrane interface.
• Generated membrane curvature through artificial buckling to study trehalose's preference for curved regions.

Main Results:

• Coarse-grained models required force-field parameter tuning for accurate trehalose-lipid interactions.
• Trehalose concentration had a weak effect on the area per lipid but increased membrane compressibility.
• Bending modulus remained unaffected by trehalose, consistent with experimental findings.
• Trehalose preferentially accumulated in highly curved regions of the lipid bilayer.

Conclusions:

• Molecular dynamics simulations provide insights into trehalose-lipid interactions and their impact on membrane properties.
• Trehalose's preference for curved membrane regions suggests a role in membrane curvature sensing and generation.
• Further refinement of CG force fields is needed for precise modeling of trehalose-membrane interactions.