Molecular Simulations Of The Deformation Kinetics Of Biomembranes And Their Interaction With Nanoparticles

The development of biological medicine is the key for the health of human beings.Biological membrane,which bridges the internal and the external cellular environments,plays an important role in various cell activities,including the exchange of materials and signal transduction.Therefore,we urgently need to understand the interaction between biological medicine and cell membrane.In this thesis we focus on the deformation kinetics of biological membranes and the interaction between membranes and nanoparticles(NPs).Computer simulation has achieved rapid development in recent years,which especially suitable for studying the complicate physiological environment of living cells.Most dynamic processes at the nanometer size that takes place in cells are hardly directly observed by the experimental techniques,whereas,they can be modeled through the computer simulation technique.Here,we employ dissipative particle dynamics(DPD)method to systematic study the interaction between NPs and biological membranes that involves several cellular activities,such as membrane fusion,material transportation and the tube pearling instability.The main contents in this work are listed as follows:1.Membrane curvature directs the assembly of NPs.The particular DPD method with an implicit water model is applied to investigate the aggregation of NPs on curved membranes.We propose that the membrane curvature can direct the interaction between the NPs and the membrane.First we demonstrate that surface tension of a cylindrical membrane tube directs the arrangement of NPs on its surface.At low surface tension,some ordered NP patterns,e.g.,the ring-like arrangement are found.Similarly,the interaction strength between the NPs and the membrane also strongly affect the arrangement of NPs:the increase of the interaction strength promotes the formation of ordered patterns of NPs.Then,we investigate how the number density,the aspect ratio and the curvature of NPs affect their assembly on the surface of membrane tubes.Moderate number density of NPs is required for the formation of ring-like shape pattern;the aspect ratio affects the NP patterns through regulating rotation direction of NPs on the membrane tube;The curvature matching between the NP and membrane tube also affect the NPs patterns.Our findings provide essential understanding of the aggregation behavior of membrane curvature proteins and the design of the targeted drug release.2.Pulling force generated by fusion proteins drives the membrane fusion.From the simulation,we propose that the pulling force generated by fusion proteins initiates the fusion process and the membrane tension regulates the subsequent fusion stages.The main conclusions in this work can be concluded as follows:the pulling force catalyzes membrane fusion.Firstly,lipid head overcrowding in the contacting region,which leading to an increase in the head-head repulsion and/or the unfavorable head-tail contacts from opposing membranes.Thus the stability of the contacting region is disturbed.Then in the area of contacting region,the realease of the surface energy lead to the membrane fusion or vesicle rupture.Our work strongly supports that the universal characteristic for the protein-mediated fusion is tight pulling and that the membrane tension plays an essential role in fusion.3.The interaction of the vesicles in the soft confinement and their transport.Here we investigate how to direct the motions of soft particles(vesicles)in the soft confinement generated by the crowded environment inside cells.We report a novel mechanism for the movement of soft particles in soft confinement through analyzing the experienced force of the vesicles,which suggest that the transport of the vesicles can be controlled by the shape deformation of the soft confinement.We show that there exist a specific dynamic pathway for the vesicles transport-the two vesicles move close to each other because of a effective attraction.4.Exploring the shape deformation of biomembrane tubes with theoretical analysis and computer simulation.The shape deformation of membrane nanotubes is studied by a combination of theoretical analysis and simulation.First,we perform free energy analysis to demonstrate the effects of various factors on two ideal states(cylindrical membrane tube and spherical vesicle)for the pearling transition,and then we carry out dissipative particle dynamics(DPD)simulation to find different models for inducing tube deformation,including the osmotic pressure,area difference and spontaneous curvature models,are considered to investigate tubular instabilities.Combined with free energy analysis,our simulations show that the origin of the deformation of membrane tubes in different models can be classified into two categories:effective spontaneous curvature and membrane tension.We further demonstrate that for different models,a positive membrane tension is required for the pearling transition.Finally we show that different models can be coupled to effectively deform the membrane tube.