Mechanical force drives the polarization and orientation of cells

Abstract

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 behavior of single cells, which has been studied intensively from many aspects (cell migration, adhesion, polarization, proliferation, etc.) and at various scales (molecular, subcellular, and cellular), the behavior of multiple cells is less well understood, particularly from a quantitative perspective. In this paper, 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 behavior of polarization and orientation provides a new perspective for understanding cell behavior in living organisms and a guideline for tissue engineering in biomedical applications.