Physical Principles Of Single Cell And Cell Organization In Extracellular Micro-environment

Traditional biological researches have been focused more on the cell chemical signals,so experiments are mainly performed in a two-dimensional culture environment.However,the extracellular microenvironment in vivo is much more complicated,including the extracellular matrix(ECM)composed of various chemical components,and heterogeneous types of cells.The cells are linked to the extracellular matrix by adhesion proteins,and the mechanical signal response resulting from stiffness sensing affects cell migration patterns,morphology and differentiation.In a cell population,the force balance between cell adhesion and cytoskeletal contraction determines many processes,such as tumor collective invasion,cell rearrangement,organ deformation,and wound healing.Extracellular matrix deformation coupling with cell migration provides an ideal mechanism for long rang mechanical signal transmission.Therefore,we study the physical behaviors of single cells and cell populations in a three-dimensional environment with the following aspects:First,breast cancer cell lines were used to analyze the different morphology and movement of single cells in 2D and quasi-3D environments.The concentration of Matrigel and cellular ECM degradation ability are changed to affect cell behaviors responding to ECM mechanical property variations.Second,the breast cyst cells are then cultured on a collagen substrate to study cell communication with mechanical signals transmitted by the collagen bundles modified during cell migration.Third,we used breast cyst cells and epithelial cells with intercellular adhesion and surface tension regulation to study the morphology and kinetics of cell monolayer.We demonstrate that cell shape factors are positively correlated with cell velocity under the same cell-cell interaction conditions.However,changing the intercellular forces will result in overall motility changes in the monolayer.Then,the coculture system in a quasi-3D environment indicated that the abnormal aggregation behavior results from the strong collective polarization of cell migration mediated by ECM mechanical coupling.To the best of our knowledge,this is the first direct observation of collective cellular dynamics induced via ECM-mediated mechanical coupling of the cells.Finally,we attempt to locate the co-culture system to the Matrigel substrate and study the behaviors of the cell population on the substrate with different stiffness.On the soft substrate,cells could aggregate into clusters even with strong cell-matrix adhesion,by ECM deformation.In summary,cell dynamics and morphology of single cells,homogeneous and heterogeneous cell populations are strongly influenced by the extracellular microenvironment.It opens the new avenues for regulation of cell collective behaviors in biological engineering.