Collective Cell Polarization,Arrangement And Migration

Cell-substrate interactions and cell-cell interactions play a crucial role(involving adhesion,arrangement,polarization,migration,differentiation,and other behaviors of collective cells during the process of tissue formation,wound healing,and cancer metastasis)in the synergistic behavior of collective cells,but the mechanism of quantitative regulation is unclear.In this dissertation,experimental studies,theoretical modeling,and molecular dynamics simulations were performed to investigate the effects of cell-substrate interactions and cell-cell interactions on the synergy of collective cells in a complex environment(including substrate stiffness,geometric constraints,and external force loading).The main research content includes:(1)A one-dimensional cell chain model was constructed on different stiffness hydrogel substrates,and the intercellular cooperation was quantitatively studied.The combination of experimental research and theoretical modeling revealed the effects of substrate stiffness,intercellular adhesion strength,and cell chain length on the synergistic contraction behavior of cell chains.At the same time,the results indicate that the intercellular coordination is regulated by the coupling of substrate stiffness and intercellular adhesion strength.(2)A uniaxially-stretched cell mechanics loading device was designed to observe the mechanical behavior of the cells in a loaded environment in real time.Using this device,the healing process of wounds with different curvature under cyclic uniaxial stretching and the corresponding cell arrangement and polarization behavior were systematically studied.The effects of stretching amplitude and stretching direction on wound healing modes and healing speed were studied.The results show that the wound healing mode is very different from the static healing mode when stretched,and the healing speed is related to the stretching amplitude.(3)Based on the uniaxially-stretched cell mechanics loading device,the effects of stretching amplitude,stretching frequency,and cell density on wound formation,wound area,wound angle,and cell arrangement angle on the epithelial cell layer were systematically studied.At the same time,a molecular dynamics model was established to study the effect of stretching amplitude on the maximum wound area.Experimental observations revealed that under tensile loading,cell division is the main cause of wound nucleation.