Living tissues often have anisotropic and heterogeneous organizations, in which developmental processes are coordinated by cells and extracellular matrix modeling. Cells have the capability of modeling matrix in long ...Living tissues often have anisotropic and heterogeneous organizations, in which developmental processes are coordinated by cells and extracellular matrix modeling. Cells have the capability of modeling matrix in long distance;however, the biophysical mechanism is largely unknown. We investigated the dynamic remodeling of collagen I (COL) fibril matrix by cell contraction with designed patterns of cell clusters. By considering cell dynamic contractions, our molecular dynamics simulations predicted the anisotropic patterns of the observed COL bundling in experiments with various geometrical patterns without spatial limitation. The pattern of COL bundling was closely related to the dynamic remodeling of fibril under cell active contraction. We showed that cell cytoskeletal integrity (actin filaments and microtubules), actomyosin contractions, and endoplasmic reticulum calcium channels acting as force generations and transductions were essential for fiber bundling inductions, and membrane mechanosensory components integrin and Piezo played critical roles as well. This study revealed the underlying mechanisms of the cell mechanics-induced matrix remodeling in large scales and the associated cellular mechanism and should provide important guidelines for tissue engineering in potential biomedical applications.展开更多
基金the National Natural Science Foundation of China(NSFC 11872129 and 12372312)the Natural Science Foundation of Jiangsu Province(BK20181416)+3 种基金Projects of“Jiangsu Specially-appointed Professor”and“Jiangsu six talent peaks(C)”(M.O.)the National Natural Science Foundation of China(11902051)(B.B.)the National Natural Science Foundation of China(11532003)(L.D.)the National Natural Science Foundation of China(11932017)(B.J.).
文摘Living tissues often have anisotropic and heterogeneous organizations, in which developmental processes are coordinated by cells and extracellular matrix modeling. Cells have the capability of modeling matrix in long distance;however, the biophysical mechanism is largely unknown. We investigated the dynamic remodeling of collagen I (COL) fibril matrix by cell contraction with designed patterns of cell clusters. By considering cell dynamic contractions, our molecular dynamics simulations predicted the anisotropic patterns of the observed COL bundling in experiments with various geometrical patterns without spatial limitation. The pattern of COL bundling was closely related to the dynamic remodeling of fibril under cell active contraction. We showed that cell cytoskeletal integrity (actin filaments and microtubules), actomyosin contractions, and endoplasmic reticulum calcium channels acting as force generations and transductions were essential for fiber bundling inductions, and membrane mechanosensory components integrin and Piezo played critical roles as well. This study revealed the underlying mechanisms of the cell mechanics-induced matrix remodeling in large scales and the associated cellular mechanism and should provide important guidelines for tissue engineering in potential biomedical applications.
