Studies On The Aggregation Of Cell-Bounci Membrane Vesicles Upon Dimethyl Sulfoxide Stimulation

Previous studies on cell bound membrane vesicles(CBMVs)revealed the physiological characteristics,microstructure of vesicles,and the dynamics of vesicles in different states.Based on the previous research,this research studied aggregation,a kind of more complicated motion of vesicles.The research involves algorithm development,quantification of biological phenomena and mechanism exploration.In the first part,analytical method system including three algorithms from simplicity to complexity were explored and then verified by simulation.First,the vesicle movement was defined by three motion modes(i.e.directed,brownian,and restricted motions)and quantified by a mathematical model.Second,a simple aggregation algorithm under a fixed threshold was established,and then the method of persistent homology based on topology was introduced to describe the globlal information on aggregation.Finally,the idea of persistent homology was optimized,and a real-time quantitative model of vesicle aggregation based on complex networks was established.Average path length,aggregation coefficient and entropy were introduced for the unity of local and global aggregation.To verify the analytical method system,computer simulation was used to simulate the aggregation behavior of particles.First,Langevin equation was used to construct a motion model,and three kinds of particle aggregation modes were simulated(i.e.local aggregation model,global aggregation model,and mixed aggregation models).Then,on this basis,we used the analytical method system for quantitative analysis.The results showed that excessive attraction in the local clustering motion model of particles caused local clustering and the loss of global connectivity.In two other cases,as the particles got closer,the parameters showed an increasing trend.In the second part,the analytical method system was applied to investigate the aggregation of CBMVs on endothelial cells(HUVECs).Via simple algorithm,it was found that 10%DMSO could increase the movement velocity and maximal displacement of CBMVs as well as the degree of vesicle aggregation.To further quantitatively analyze vesicle aggregation,the algorithms established in the first part were recruited.The data showed that 10%DMSO induced the increase in average size of vesicle clusters and the decrease in the ratio of cluster number to total vesicle number on cell surfaces.?₀(the topological quantity describing the number of isolated components)decreased at low filter radius,and the global clustering coefficient increased significantly.On the other hand,we found that 10%DMSO(1 h)also induced the re-distribution of intracellular nitric oxide(NO)into CBMVs in company with the increase of intracellular reactive oxygen species(ROS),implying the potential correlationship between vesicle aggregation and oxidative stress which is closely correlated to mitochondria.By exploring the interaction between cell surface vesicles and mitochondria,it may be possible to preliminarily reveal the mechanism of CBMV aggregation.Therefore,we carried out the third part of the research.In the third part,on basis of Ising model,we established a model for evaluating the interaction between two types of organelles,and applied it to explore the interaction between cell bound membrane vesicles and mitochondria.It was found that upon DMSO stimulation,the interaction between cell surface vesicles and mitochondria became stronger,implying the potential function of CBMVs in regulating cell oxidative stress.Taken together,algorithms for quantifying vesicle aggregation were developed in this study,based on which the DMSO-induced aggregation of cell-bound membrane vesicles on cells was quantitatively analyzed.Subsequently,the interaction between CBMVs and mitochondria was evaluated via a modified model.the data revealed that vesicle aggregation is potentially correlated with oxidative stress.This study is of great significance for further revealing the function of vesicles in the future.It provides a new perspective for the quantification of the movement of substances in cells.This research is multidisciplinary.