Mechanical Force Drives the Polarization and Orientation of Collective Cells
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摘要
Collective cell groups are organized to form specific patterns that play an important role in various physiological and pathological processes,such as tissue morphogenesis,wound healing,and cancer invasion.Compared to the behaviors of single cells that have been studied intensively from many aspects(cell migration,adhesion,polarization,proliferation,etc.)and at various length scales(molecular,subcellular,and cellular),the behaviors of multiple cells are less well understood,particularly from a quantitative perspective.In this talk,we present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling,including cell behavior on/in 2D and 3D substrate/tissue.We find that collective cell behavior,including polarization,alignment,and migration,is closely related to local stress states in cell layers or tissue,which demonstrates the crucial role of mechanical forces in living organisms.Specifically,cells demonstrate preferential polarization and alignment along the maximum principal stress in the cell layer,and the cell aspect ratio increases with in-plane maximum shear stress,suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation.This theory of stress-driven cell behaviors of polarization and orientation provides a new perspective for understanding cell behaviors in living organisms and a guideline for tissue engineering in potential biomedical applications.Strikingly,we note that with regard to the polarization and alignment of collective cells,a typical feature of cell morphology is that the cells generally align along the edge of the pattern,which was called edge effect or boundary effect by assuming that the edge plays a role in cell alignment due to a phenomenon of chemistry.However,the edge effect is an obscure explanation.Here we showed that the edge effect could be explained by the theory of stress-driven cell behavior,i.e.,inplane stress-driven cell polarization and alignment.That is,the cell layer has a stress-free boundary condition at the edge,and thus the direction of the maximum principal stress should be precisely along the edge.According to the theory of stress-driven cell polarity,the cells then preferentially align with the edge of the cell layer,independently of the geometry of the pattern.Once there is a force-free condition at the edge or the boundary,the cells align along the edge of the pattern.Otherwise,the cell may not align with the edge; for example,the cells preferentially align in the radial direction of the wound because of the presence of the contractile force by the actin ring at the wound edge,which is in contradiction with the so-called edge effect but consistent with our theory of stress-driven cell polarity.
Collective cell groups are organized to form specific patterns that play an important role in various physiological and pathological processes,such as tissue morphogenesis,wound healing,and cancer invasion.Compared to the behaviors of single cells that have been studied intensively from many aspects(cell migration,adhesion,polarization,proliferation,etc.)and at various length scales(molecular,subcellular,and cellular),the behaviors of multiple cells are less well understood,particularly from a quantitative perspective.In this talk,we present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling,including cell behavior on/in 2D and 3D substrate/tissue.We find that collective cell behavior,including polarization,alignment,and migration,is closely related to local stress states in cell layers or tissue,which demonstrates the crucial role of mechanical forces in living organisms.Specifically,cells demonstrate preferential polarization and alignment along the maximum principal stress in the cell layer,and the cell aspect ratio increases with in-plane maximum shear stress,suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation.This theory of stress-driven cell behaviors of polarization and orientation provides a new perspective for understanding cell behaviors in living organisms and a guideline for tissue engineering in potential biomedical applications.Strikingly,we note that with regard to the polarization and alignment of collective cells,a typical feature of cell morphology is that the cells generally align along the edge of the pattern,which was called edge effect or boundary effect by assuming that the edge plays a role in cell alignment due to a phenomenon of chemistry.However,the edge effect is an obscure explanation.Here we showed that the edge effect could be explained by the theory of stress-driven cell behavior,i.e.,inplane stress-driven cell polarization and alignment.That is,the cell layer has a stress-free boundary condition at the edge,and thus the direction of the maximum principal stress should be precisely along the edge.According to the theory of stress-driven cell polarity,the cells then preferentially align with the edge of the cell layer,independently of the geometry of the pattern.Once there is a force-free condition at the edge or the boundary,the cells align along the edge of the pattern.Otherwise,the cell may not align with the edge; for example,the cells preferentially align in the radial direction of the wound because of the presence of the contractile force by the actin ring at the wound edge,which is in contradiction with the so-called edge effect but consistent with our theory of stress-driven cell polarity.
Collective cell groups are organized to form specific patterns that play an important role in various physiological and pathological processes,such as tissue morphogenesis,wound healing,and cancer invasion.Compared to the behaviors of single cells that have been studied intensively from many aspects(cell migration,adhesion,polarization,proliferation,etc.)and at various length scales(molecular,subcellular,and cellular),the behaviors of multiple cells are less well understood,particularly from a quantitative perspective.In this talk,we present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling,including cell behavior on/in 2D and 3D substrate/tissue.We find that collective cell behavior,including polarization,alignment,and migration,is closely related to local stress states in cell layers or tissue,which demonstrates the crucial role of mechanical forces in living organisms.Specifically,cells demonstrate preferential polarization and alignment along the maximum principal stress in the cell layer,and the cell aspect ratio increases with in-plane maximum shear stress,suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation.This theory of stress-driven cell behaviors of polarization and orientation provides a new perspective for understanding cell behaviors in living organisms and a guideline for tissue engineering in potential biomedical applications.Strikingly,we note that with regard to the polarization and alignment of collective cells,a typical feature of cell morphology is that the cells generally align along the edge of the pattern,which was called edge effect or boundary effect by assuming that the edge plays a role in cell alignment due to a phenomenon of chemistry.However,the edge effect is an obscure explanation.Here we showed that the edge effect could be explained by the theory of stress-driven cell behavior,i.e.,inplane stress-driven cell polarization and alignment.That is,the cell layer has a stress-free boundary condition at the edge,and thus the direction of the maximum principal stress should be precisely along the edge.According to the theory of stress-driven cell polarity,the cells then preferentially align with the edge of the cell layer,independently of the geometry of the pattern.Once there is a force-free condition at the edge or the boundary,the cells align along the edge of the pattern.Otherwise,the cell may not align with the edge; for example,the cells preferentially align in the radial direction of the wound because of the presence of the contractile force by the actin ring at the wound edge,which is in contradiction with the so-called edge effect but consistent with our theory of stress-driven cell polarity.
引文
[1] He,S.; Liu,C.; Li,X.; Ma,S.; Huo,B.; Ji,B. Dissecting Collective Cell Behavior in Polarization and Alignment on Micropatterned Substrates. Biophysical Journal 2015,109:489-500.
[2] Li,X.; He,S.; Xu,J.; Li,P.; Ji,B. Cooperative Contraction Behaviors of a One-Dimensional Cell Chain. Biophysical Journal2018,115:554-564.
[3] He,S.; Li,X.; Ji,B. Mechanical Force Drives the Polarization and Orientation of Cells. Acta Mech Sin 2019,35:275-288.
[4] Liu,C.; Xu,J.; He,S.; Zhang,W.; Li,H.; Huo,B.; Ji,B. Collective Cell Polarization and Alignment on Curved Surfaces. Journal of the Mechanical Behavior of Biomedical Materials 2018,88:330-339.
[2] Li,X.; He,S.; Xu,J.; Li,P.; Ji,B. Cooperative Contraction Behaviors of a One-Dimensional Cell Chain. Biophysical Journal2018,115:554-564.
[3] He,S.; Li,X.; Ji,B. Mechanical Force Drives the Polarization and Orientation of Cells. Acta Mech Sin 2019,35:275-288.
[4] Liu,C.; Xu,J.; He,S.; Zhang,W.; Li,H.; Huo,B.; Ji,B. Collective Cell Polarization and Alignment on Curved Surfaces. Journal of the Mechanical Behavior of Biomedical Materials 2018,88:330-339.