AFM Study On The Interaction Between β-amyloid Protein And Phospholipid Membrane

Alzheimer’s disease is a neurodegenerative disease with high incidence.The clinical manifestations include memory loss,progressive cognitive decline,accompanied by various abnormal mental behavior and personality changes,which seriously affect the quality of life of the patients.Data shows that after heart disease,malignant tumors,and stroke,Alzheimer’s disease has become the fourth leading cause of death among the elderly.Regarding the pathogenesis of Alzheimer’s disease,it is generally believed thatβ-amyloid protein induces cell toxicity through interaction with cell membranes.However,there are still many unsolved problems regarding the mechanism of the interaction between them,so it is necessary to understand the mode of action and influencing factors ofβ-amyloid and cell membrane deeply.In this article,we started with the mechanical properties of cell membranes to study the effects of changes in cell membrane mechanical properties on the action ofβ-amyloid and cell membranes.Theβ-amyloid protein used in this paper is Aβ_1-42,and the POPC phospholipid membrane was selected to simulate the cell membrane,and the mechanical properties of the phospholipid membrane were adjusted by adding cholesterol to the phospholipid membrane.We measured the mechanical properties of the phospholipid membrane before and after the action of the two,and the influence of the interaction between the two on the mechanical properties of the phospholipid membrane was studied.The experimental results showed that when the cholesterol content in the POPC membrane increased,the compressive force of the membrane increased,that was,the membrane elasticity increased.When the POPC phospholipid membrane interacted with Aβ_1-42,Aβ_1-42 destroyed the surface structure of the phospholipid membrane,resulting in a decrease in the compressive force of the phospholipid membrane,that was,the elasticity of the membrane.Compared with the pure POPC phospholipid membrane,when the molar concentration of cholesterol is 10%,the POPC phospholipid membrane is more likely to be destroyed when it interacted with Aβ_1-42,because the addition of cholesterol increased the ZETA potential of the POPC membrane and enhanced the static electricity between membrane and Aβ_1-42,so the membrane is damaged more seriously.However,when the molar concentration of cholesterol was 20%and 30%,the destruction of POPC phospholipid membrane by Aβ_1-42 was weakened.This is because when the cholesterol content in the POPC membrane is higher,although the electrostatic interaction between the membrane and Aβ_1-42 is enhanced,the interatomic interaction in the POPC phospholipid membrane is also enhanced,the rigidity and stability of the membrane were stronger,and enhanced the electrostatic interaction but not enough to destroy the POPC phospholipid membrane.This article also used atomic force microscopy to characterize the changes in surface structure before and after the interaction between POPC phospholipid membrane and Aβ_1-42.After the action of pure POPC phospholipid membrane and 10%molar ratio of cholesterol between POPC phospholipid membrane and Aβ_1-42,holes appear on the surface of phospholipid membrane,the action mode of Aβ_1-42 and phospholipid membrane was“detergent action”mode.When the molar content of cholesterol in the POPC phospholipid membrane is 10%,the number of pores on the surface of the phospholipid membrane increased and the diameter of the pores increased after the action of the two,indicating that Aβ_1-42 has a stronger effect on the destruction of the phospholipid membrane.After the POPC phospholipid membrane with a molar cholesterol content of 20%interacted with Aβ_1-42,part of Aβ_1-42 extracted the phospholipid molecules in the phospholipid bilayer,forming a pore structure in the membrane,and part of Aβ_1-42 in the form of spherical oligomers Gathered on the surface of the POPC phospholipid membrane,at this time,the mode of action of Aβ_1-42 and POPC phospholipid membrane had both a“detergent effect”mode and a“carpet mode”mode.After the POPC phospholipid membrane with a molar cholesterol content of 30%interacted with Aβ_1-42,there was no obvious downward depression on the surface.Aβ_1-42 mainly gathered on the surface of the phospholipid membrane in the form of spherical oligomers.At this time,Aβ_1-42 and POPC The mode of action of phospholipid membrane was mainly"carpet mode"mode.In summary,changes in the mechanical properties of cell membranes are an important cause ofβ-amyloid attacking cell membranes.The research in this thesis has important theoretical value for understanding the toxicity mechanism of β-amyloid protein.