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- Type of Document: Ph.D. Dissertation
- Language: Farsi
- Document No: 58064 (48)
- University: Sharif University of Technology
- Department: Institute for Nanoscience and Nanotechnology
- Advisor(s): Ejtehadi, Reza; Vossoughi, Manoochehr
- Abstract:
- To use protein nanocages in pharmaceutical and medical applications, it is necessary to adjust the dose of nanocages inside the membrane vesicles with proper accuracy. Since the packaging of several nanocages inside a vesicle is always associated with a range of sizes, our suggestion is to adjust the system parameters to reach the condition that engulfing occurs for each nanocages and each nanocages is packed inside a vesicle. The interaction energy between a membrane and a protein is one of the important parameters that effectively affects packing efficiency. The effect of this factor on the cooperative behavior of the protein and membrane at the coarse-grain level, as well as their correlated behavior at the atomic scale, was investigated using molecular dynamics. This atomic-scale study resulted in the proposal of a novel mechanism explaining the membrane’s curvature induction process. According to this mechanism, at atomic scale with the increase in the interaction between the protein and the membrane, the correlative behavior of PIP2 lipids with the membrane increases. This process will produce regions rich in this kind of lipid surrounding the protein absorbent spots and cause the middle spaces between the points to empty, which will cause the membrane to develop a negative curvature. The findings of this study revealed that strengthening the binding interaction between the protein and the membrane improves the quality of this occurrence and enhances the curvature formed in the membrane. However, at the coarse-grained scale, an increase in interaction energy is associated with an increase in Casimir forces and the dynamics of indentation in the membrane. The dynamics of indentation in the membrane accelerates with an increase in interaction energy at lower concentrations (132 protein/µm2), until at ϵ = 1.8, it finally outpaces the induced displacement dynamics brought on by Casimir forces. This phenomenon cannot occur at higher concentrations (1190 protein/µm2), because of the higher density of proteins per unit area. Nevertheless, multiple nanocages are still packed into a single vesicle. Since the concentration of 132 protein/µm2 is the same as what we encounter in the laboratory environment, it is reasonable to assume each nanocage packing in a single vesicle if a module can be employed in the manufacturing of protein nanocages that creates the mentioned interaction circumstances in the system
- Keywords:
- Casimir Force ; Vesicle Curvature ; Nanocages ; Membrane Bending Mechanism ; Membrane-Protein Interaction ; Vesicle Packaging ; Self Assembly
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