Coarse-grained Simulation Of The Interaction Of Phospholipid Membrane With Cell-penetrating Peptide And C₆₀

Advanced mammalian cell membrane is a complex body composed of proteins,lipids,cholesterol and sugars.The cell membrane is highly asymmetric and the distribution of various components on the membrane is asymmetric.Cell membrane plays an important role in substance transport,energy transfer,metabolic regulation and so on.In medicine,many diseases are closely related to changes in membrane composition.Therefore,it is significant to understand the structure and properties of cell membrane and its interaction with external substances.In this paper,we study the effect of cholesterol concentration on asymmetric erythrocyte membrane by the coarse-grained molecular dynamics method,and analyze the interaction mechanism of the external substances cell-penetrating peptides and C₆₀ with asymmetric membrane.It provides some theoretical guidance for drug design and transportation.In chapter 1,we briefly introduce the composition,structure and kinetic properties of cell membrane in higher mammals.Then,we Introduce classification and application of cell-penetrating peptides and their access to cells and research progress on the interaction between membrane peptide and phospholipid membrane.We briefly introduce C₆₀ and its application prospects,lipid membrane and C₆₀ interaction mechanism and research progress.In chapter 2,we mainly introduce the coarse-grained molecular dynamics method.Firstly,the development of coarse-grained molecular dynamics method,MARTINI coarse-grained force field and MARTINI model are introduced briefly.Then the parameters of interaction between particles in MARTINI force field and the setting of simulation parameters are introduced.Finally,we introduce the coarse-grained model used in this paper.In chapter 3,this is the first part of the main research.Cholesterol is widely found in the cell membrane of higher mammals.The change of cholesterol concentration is closely related to some diseases,such as cardiovascular and cerebrovascular diseases atherosclerosis.Cholesterol-induced changes in cell membrane structure and kinetic properties are a hot topic.Based on the model of human erythrocyte membrane,the effect of cholesterol concentration on asymmetric phospholipid membrane is investigated by method of coarse-grained molecular dynamics.Our results show that the increase of cholesterol concentration can increase the thickness of lipid membrane and the tail order parameter of phospholipid.The increase of cholesterol concentration also can decrease the average surface area of lipids and the transverse diffusion rate of lipid.Cholesterol concentration also affects the flip-flop of cholesterol molecules between bilayers of phospholipid.These results may be helpful in improving the understanding of the structure and kinetic properties of cholesterol-containing lipid membranes.In chapter 4,this is the second part of the main research.Cell penetrating peptides can"carry"drug molecules,proteins and so on into the cells,thus effectively killing the diseased cells.Cell penetrating peptides have a broad application prospect in clinical medicine.Based on coarse-grained molecular dynamics method,we explore the interaction between the Arg9peptides and the asymmetric lipid membrane.The results show that because of the existence of high energy barrier in phospholipid membrane,a single Arg9 peptide cannot penetrate the phospholipid membrane,and only when the ratio of the peptide to membrane reached a certain proportion,a certain number of Arg9 peptides will enter the cytoplasm.We analyze the reason for this phenomenon in detail,which is caused by the enhanced coulomb interaction and the synergistic effect between the peptides and the phospholipid membrane.This study can better help understand the mechanism of membrane penetration and provide some theoretical guidance for drug delivery.In chapter 5,as the third part of the study,we analyze the interaction between the nano-material C₆₀ and asymmetric lipid membrane.C₆₀ has many excellent properties and potential important applications in the field of biomedicine.We study the effect of cholesterol concentration on the entry of C₆₀ into asymmetric lipid membranes.The results show that cholesterol concentration affect the diffusion of C₆₀0 in lipid membrane.At the same time,C₆₀has a influence on the structure of lipid membrane,but it does not lead to the rupture of the lipid membrane.The addition of C₆₀ increases the surface area of lipid molecule,decreases the plasma membrane thickness and the tail order parameter of phospholipid and the difference of cholesterol concentration also affects the change of these parameters.In chapter 6,we summarize the work of this paper and also look forward to the future work.