Research And Application Of Interactions Between Micro/Nano-Particles And Lipids

Phospholipids are the major component of biomembranes and constitute the skeleton of cell membrane. The study of the system containing a single or several kinds of phospholipids can help to understand the extremely complex biofilm system. It can also reveal physicochemical properties and functional accomplishing means of biomembranes. While the research into the interactions between micro-and nano-particles (natural or synthetic nanoparticles, proteins, polymers, viruses, et al.) and phospholipid systems is helpful to understand the complex intracellular life activities. It can also give a practical guide to the design of artificial organs and proteins, drug delivery devices, and has been widely applied in many important areas such as life science, materials science and medical science.In1st chapter, we introduced the compositions, structure and functions of biomembrane together with the structure and characteristics of phospholipid molecules; Then we mainly introduced interactions between the widely accepted and applied artificial membrane models and micro/nano-materials, like nanoparticles, peptides and carbon nanotubes.In2nd chapter, we introduced the main instruments used in this thesis-Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) and Laser Scanning Confocal Microscope (Confocal). We also introduced the computer simulation method used in the thesis-Dissipative Particle Dynamics (DPD). QCM-D technique is one of the most effective methods to monitor the dynamic behaviors of a layer on a solid surface. Moreover, it has been reported recently that it is able to provide a fingerprint for the peptide-membrane interactions. Confocal has excellent resolution (-180nm) and remarkable three-dimensional reconstruction function. It is one of the most important imaging techniques applied in bioresearches. DPD is an coarse-gained mesoscopic simulation method. It can simulate the system that spans a large simulation time and space scale, and contains a mass of molecules. It has been extensively employed in the study of biomembrane systems.In3rd chapter, mesoporous silica nanoparticles (MSN) with cationic and anionic surficial charges were synthesized and their adsorption behaviors onto supported lipid membrane at different pH values were also studied by QCM-D. We found that NH2-MSN could be adsorbed onto the membrane from pH4to8, while the adsorption of COOH-MSN to the membrane could not occur due to its charge is always the same with that of the membrane at any pH values. These results might provide information for understanding and predicting the interactions between nanoparticles and cell membranes, and could be effectively used in drug delivery systems and disease treatment.In4th chapter, the molecular-level interactions of an antimicrobial peptide melittin with supported membrane were studied by the combination of dissipative quartz crystal microbalance(QCM-D) experiments and computer simulations. We found the response behavior of lipids upon peptide adsorption greatly influence their interactions. The perturbance and reorientation of the lipid in liquid phase facilitate the insertion of melittin in a trans-membrane way, but in solid phase, asymmetrical membrane disruption happens. Apart from the lipid state, the local peptide-to-lipid ratio also affects the insertion capacity of melittin. When the local peptide number density is high, adjacent peptides can cooperatively penetrate into the membrane. This observation explains the occurrence of the conventional "carpet" mechanism. Furthermore, this work might be a good example of the application of QCM-D for the exploration of membrane-active peptides.In5th chapter, QCM-D technique combined with computer simulations was employed to investigate the deposition and transformation of vesicles, as well as the subsequent membrane-melittin interactions on different substrates. A range of substrate surfaces, i.e. naked SiO2without or with Au/polyelectrolyte coating, were produced. The nature of the substrate determined whether the adsorbed vesicles were present as a high-quality supported bilayer or an assembled vesicle matrix, which consequently influenced the membrane-melittin interactions. It was indicated by the related computer simulations that the lipid packing state of the membrane was a key factor to determine the mechanism of membrane-peptide interactions.In6th chapter, we, for the first time, fabricated a type of "smart" complex, namely a lipid-incorporated and pNIPAM particle-based lipogel by a solvent-exchange method and regulated the morphology by controlling the phase transition of the pNIPAM microgel particles. At room temperature the lipogel particle takes on a sun-like structure containing a spherical hierarchical scaffold surrounded with a layer of lipid assemblies. The thermo-sensitive phase transition and volume contraction properties of pNIPAM allowed us to dynamically and reversibly modulate the morphology and structure of the lipogel, between the sun-like construction and a contracted pNIPAM-lipid hybrid sphere. By contrast, the rapid and dramatic phase transition of pNIPAM under salt addition triggered the breakaway and release of the adsorbed assemblies of lipogel to bulk solution, which can be repeated by adjusting the salt content in the buffer solution. Then we demonstrated the temperature-triggered drug release behavior and moreover the tunable drug loading and release capacities of the lipogel. At the room temperature of22℃, no calcein was released from the lipogel over time; while at the body temperature, the release process was significantly promoted, during which lipids acted as drug holders on the basis of the pNIPAM scaffold carrier and prolonged the release process from10minutes to a much longer time of2hours. Furthermore, based on the salt-induced lipid-release behavior of the lipogel, the relative amount of lipids incorporated in the lipogel was roughly modulated. As a result, the loading capacity and release kinetics of calcein was effectively controlled.In7th chapter, we summarized the thesis and described the prospect of work.