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题名 细胞-微纳米材料相互作用的统计热力学机理研究
姓名 李珑
院系 土木工程与力学学院
专业 工程力学
学位名称 工学博士
外文题名 Research on Mechanism of Thermodynamics in Cell-Micro/NanoMaterial Interactions
第一导师姓名 王记增
关键词 连续介质力学;统计力学;受体介导内吞;噬菌体;蠕虫链模型;摩擦系数;渗透压抑制;细胞粘附;加载率;粘附强度
外文关键词 continuum mechanics;statistic mechanics;receptor-mediated endocytosis;bacteriophage;wormlike chain model;friction coefficient;osmotic pressure inhibition;cell adhesion;loading rate;adhesion strength
学科 工学
摘要 细胞-微纳米材料相互作用在机体的生理与病理过程中扮演着重要的角色,研究细胞-微纳米材料间相互作用在自然基础科学和生物医药工程等领域中现已成为热点问题。然而,如何理解复杂因素间的耦合作用是研究细胞-微纳米材料相互作用中力学机制的关键所在。本博士学位论文针对这一复杂问题,开展如下工作: (1)考虑细胞骨架与细胞膜变形,受体分子扩散,受体与配体分子化学反应的耦合,研究了细胞摄入纳米颗粒机制对细胞表面自由受体与纳米颗粒表面配体初始密度比的依赖性,发现了:a)受体扩散主导机制;b)受体扩散-骨架变形耦合主导机制;c)骨架蠕变主导机制。 (2)针对噬菌体壳包裹与喷出DNA这一生理学现象,基于半柔性链聚合物分子理论与流体力学层流理论,定量地分析了DNA链从噬菌体内喷入胞外缓冲溶液的动力学过程,预测的DNA喷出长度与速度、时间关系和相关实验结果一致。 (3)考虑细胞骨架的粘弹性变形、基底的弹性变形以及受体-配体特异性分子的动力学反应过程,建立了随机-粘弹性耦合的细胞粘附模型,研究了骨架粘性对细胞粘附的影响,发现了骨架粘性越大受体-配体分子键的存活时间越久,发现了受体-配体分子键的断开趋势是由粘附边缘向粘附中心扩展。
外文摘要 The interaction between cell and micro/nanomaterial plays an important role in physiological and pathological processes of organism, such as cellular uptake of nanoparticle via recepoter-mediated endocytosis, cell adhesion and infecting host bacteria with phage. Hence, the physical mechanism of cell-micro/nanomaterial interaction is of great interest to advancing our fundamental biological understandings as well as many pratical applications in fields such as drug delivery. However, there are many complex biophysical factors involving in cell-micro/nanomaterial interaction, such as deformations of cell membrane and cytoskeleton, diffusion of mobile receptor on the cell membrane, stochastic reaction between receptor and ligand, DNA chain thermal disturbance and elastic deformation of matrix and viral capsid. To enable research on the mechanical mechanism of cell-materials interaction, it is essential to understand the underlying coupling mechanism of such complex biophysical factors. Therefore, in this thesis, we make an attempt to address this issue by developing a series of coupled cell-micro/nanomaterial interaction models based on continuum mechanics and statistical mechanics. Using these models gives some results as following:(1) By considering the coupled effects of cell membrane and cytoskeleton deformation, receptor diffusion, ligand-receptor binding, we suggested a coupled elasticity-diffusion model of cellular uptake of nanoparticles (NPs) based on continuum mechanics and statistical mechanics. We show the different regimes on cellular uptake of NPs recognized in terms of normalized initial receptor density, such as receptor diffusion-limited, receptor diffusion and cytoskeleton deformation-limited, cytoskeleton deformation-limited. The dymanics of cylinder NPs entey into cells is analysised. CNPs preferred or tended to vertically attack target cells until they are stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that show much faster initial engulfing speeds that horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. In the cased of combining impact of receptor diffusion and cytoskeleton deformation, the resistance to NPs entry into cells is described. It is also found that the cytoskeleton creep affects the cellular uptake of NPs if the re...
研究领域 分子与细胞生物力学
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