Research On Mechanism Of Thermodynamics In Cell-Micro/NanoMaterial Interactions

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 receptor density is high enough in the binding area.(2) By considering the receptor-ligand binding and cell membrane and cytoskeleton elastic deformation, we quantitatively analyze the resistance to virus entry into host cells from the view of energy. It is shown that for the enveloped virus entry into host cells, the binding energy of the receptor-ligand complex can drive the engulfment of the viral particle to overcome the resistance alternatively dominated by the membrane deformation and cytoskeleton deformation at a different engulfing stage. This is contrary to the conclusions by previous study that the cytoskeleton deformation is always dominant.(3) When receptors are densely distributed around the binding site so that receptor recruiting through diffusion is no longer energetically favorable, we thus hypothesize that another effect, the creep deformation of cytoskeleton, might turn to play the dominant role in relaxing the engulfing process. Here, we develop a creep model of cellular uptake of nanoparticles. The dynamic process of NPs engulfment retarted by the creep deformation of cytoskeleton and driven by the binding of ligand-receptor bonds after overcoming resistance from elastic deformation of lipid membrane and cytoskeleton. Based on this model, we also find an optimal NPs size corresponding to the smallest wrapping time. The result about optimal size is well agreement with previous experimental observation.(4) For a physiological phenomenon that bacteriophage could pack and eject DNA chains, based on semiflexible polyer chain theory and theory of laminar flow, we obstain statistical thermodynamic configuration of compressed wormlike chain confined into a tube. The analytical expression about viscous friction of compressed wormlike chain moving out of confined space is obtained. Moreover, we quantificationally analyze the dynamic process of DNA chain ejection from bacteriophage to external buffer solution. The theoretically predicted relations between the ejection speed, ejection time, ejection length, and other physical parameters, such as the phage type, total genome length and ionic state of external buffer solutions, show excellent agreement with in vitro experimental obsercations in the literature.(5) By combining continuum mechanics, we develop a liner elastic phage packaging and ejection DNA model. Based on variational method, the quilibrium state of system is obtained. The effects of phage elasticity on packaging force and DNA ejection dynamics are quantificationally investigated. We can also find the Young’s modulus of the phage capsid has weak effect on the DNA packaging force for the buffer with low ionic strength, but strong effect on the DNA packaging force for the buffer with high ionic strenth. Moreover, the theoretically predicted results are found to agree very well with in vitro experimental obsercations in the literature.(6) We propose a combined nonlinear continuum and statistical mechanics model by considering the effects of DNA bending deformation, electrostatic repulsion between DNA-DNA strands, and elastic deformation of phage capsid to investigate the coupled process between capsid and DNA in packaging and ejection. Based on this model, we show that packaging DNA into immature λ phage capsid uses less force than packaging DNA into mature λ. phage because of the deformability and softness of the former. Consequently, resistance to DNA packaging inside capsid decrease compared with mature ones. We also observe relationships between phage capsid size and the maximum shear stress on the inner surface of capsid and required osmotic pressure for the complete inhibition of DNA ejection. An optimized radius of capsid, around 30 nm, is found for both stable DNA packaging and effective viral infection, which may result from physical evolution.(7) For a physiological phenomenon of cell adhesion, by considering the viscoelastic deformation of cytoskeleton, elastic deformation of substrate and stochastic reaction between receptor and ligand moleculars, we propose a coupling stochastic-viscoelastic cell adhesion model. Based on this model, we investigate the effect of cytoskeleton viscoelasticity on cell adhesion. It is found that the larger value of viscosity corresponds to the longer lifetime of receptor-ligand bonds. Moreover, the trend of receptor-ligand bonds creaking is from adhesion edges to center. Moreover, the loading rate-dependent adhesion strength in cell adhesion is quantificationally analyzed. It is also shown that the high loading rate corresonds to the larger adhesion strength. However, the adhesion strength closes to a constant with decreasing the loading rate.