Molecular Dynamics Study On The Mechanical Properties Of The Interaction Between β-amyloid And Cell Membrane

Alzheimer’s disease（AD）is a chronic neurodegenerative disease with a high incidence.The clinical manifestations are memory loss,progressive cognitive decline,and various mental and behavioral abnormalities and personality changes.Affect the quality of life of patients.A large number of research results indicate that the cytotoxicity induced byβ-amyloid is the main factor,and its mechanism of action is very complicated.As the surface in direct contact with Aβamyloid,mechanical properties of cell membrane will affect the aggregation and interaction ofβ-amyloid.Therefore,molecular dynamics are used to research the interaction betweenβ-amyloid and cell membranes with different mechanical properties,and conclusions are as follows:（1）By modifying the potential well constant of the Lennard-Jones potential of the lipid atom in the CHARMM36 force field,five lipid membranes are obtained and their elastic parameters are measured.Studies have shown that as the potential well constant increases,the elastic modulus of the lipid film increases,and the tensile modulus increases.（2）The interaction between Aβ_17-42（p3 peptide）and five lipid membranes was studied,and the results showed that the interaction between Aβ_17-42（p3 peptide）and the lipid membrane depends on the mechanical properties of the lipid membrane.When the lipid membrane has moderate elasticity（the elastic modulus between 250m N/m-1500m N/m）,residue 42 has a strong electrostatic interaction with the lipid membrane,causing the lipid head to be opened.The 31-35 residues of the p3 peptide interact strongly with the lipid membrane van der Waals and insert into the lipid hydrophobic region.When the elasticity of the lipid membrane is very small or large（the elastic modulus is 130m N/m and 2250m N/m）,p3 peptide will not be inserted into the lipid membrane,which means that when the elastic modulus of the lipid membrane is within a certain range,p3 will be inserted into lipid membrane,below or above this range p3will only deposit on the membrane surface.In addition,regardless of whether the p3peptide is inserted or not,the interaction between the p3 peptide and the lipid membrane is always accompanied by the transformation of theβ-sheet structure in the p3 peptide to the coil structure.（3）The interaction between Aβ_17-42（p3 peptide 31-42 fragment）and five lipid membranes was studied,it was found the 31-42 fragment of p3 peptide is easier to interact with and enter the lipid membrane than the p3 peptide.The results showed that when lipid membrane has moderate elasticity（elastic modulus between 250m N/m-1500m N/m）,residue 42 has a strong electrostatic interaction with the lipid membrane,opening the lipid head.Especially when the elasticity is 250m N/m,the insertion of residue 31 is deeper and produces a greater van der Waals interaction.When the elastic modulus is very small or large（the elastic modulus is 130m N/m and 2250m N/m）,the31-42 fragment of p3 peptide can also interact with the lipid membrane and open the lipid head,but the depth of entry is shallow.In the process of the interaction between the 31-42 fragment of p3 peptide and the lipid membrane,theβ-sheet structure is also transformed to the coil structure.