Cell-Substrate Interaction And Cell-Cell Interaction And Their Roles In Cell Mechanosensing Behaviors

Cell-matrix interaction and cell-cell interaction play crucial roles in physiological and pathological processes,including cell adhesion,migration,polarization,tissue morphogenesis,and so on.A growing body of evidence shows that these two interactions can regulate various cell mechanosensing behaviors,but the quantitative mechanisms are still elusive.In this thesis,the mechanical modeling at different scales(subcellular,cellular and multiple cellular scales)were employed to study the effects of ECM properties(stiffness,thickness,geometry and curvature)on cell-substrate interaction and cell-cell interaction,and then their effect on cell mechanosensing behaviors.The main findings of this thesis are summarized as follows:(1)A mechanical model of protrusion and retraction of lamellipodium(LP)was developed.The effects of substrate rigidity and cell membrane tension on protrusion and retraction processes of LP were formulated.We showed that the substrate rigidity and membrane tension together regulate the LP movement.Our predictions in general agree with the experiments on cell mechanosensing behaviors at the LP and cellular levels.(2)A contraction disk model of cell-substrate interaction was developed.A traction-distance law was obtained for the distribution of traction between cell and matrix,which is of crucial importance for understanding the cell mechanosensing behaviors,including regulation of cell adhesion and migration.We found that the traction biphasically depends on the substrate rigidity.These results shed light on an existing debate on whether cells sense mechanical force or deformation when interacting with their surroundings,and indicate that cell adhesion and migration behaviors can be regulated by cell shape and substrate stiffness(3)A cell-layer interacting with substrate was studied.And the driving force of cell polarization and alignment was identified.We showed that cells prefer to polarize and align along the direction of the maximum principal stress,and the driving force of cell polarization and alignment is the in-plane maximal shear stress in cell layer.Moreover,the quantitative relation of cell polarization and alignment with the in-plane maximal shear stress on micropatterned substrates was predicted.(4)A mechanical model of cell-layer on the substrate with curvature was developed.The effects of curvature on cell-matrix interaction and cell-cell interaction were studied,and cell polarization and alignment on curved substrate were predicted.In summary,our studies showed that cell-matrix interaction(cell traction)and cell-cell interaction(the stress in cell layer)are the two critical mechanical signals that regulate the cell mechanosensing behaviors,including cell adhesion,cell spreading,cell migration,cell polarization and alignment,etc.