Cell motion-coordinated fibrillar assembly of soluble collagen I to promote MDCK cell branching formation

Abstract

Extracellular Matrix (ECM) assembly and remodeling are critical physiological events in vivo, and abnormal ECM assembly or remodeling is related to pathological conditions such as osteoarthritis, fibrosis, cancers, and genetic diseases. ECM assembly/remodeling driven by cells represents more physiological processes.Collagen I (COL) is very abundant in tissues, which assembly/remodeling is mediated by biochemical and mechanical factors. How cells regulate COL assembly biomechanically still remains to be well understood. Here we used fluorescent COL in the medium to study how cells assembled ECM which represents more physiological structures. The results showed that MDCK cells actively recruited COL from the medium and helped assemble the fibers, which in turn facilitated cell branching morphogenesis, both displaying high spatial associations and mutual dependency.Inhibition of cellular contraction force by ROCK and Myosin II inhibitors attenuated but did not block the COL fiber formation, while cell motion showed high consistency with the fiber assembly. Under ROCK or Myosin II inhibition, further analysis indicated high correlation between local cell movement and COL fiber strength as quantified from different regions of the same groups. Blocking cell motion by actin cytoskeleton disruption completely inhibited the fiber formation. These suggest that cell motion coordinated COL fiber assembly from the medium, possibly through generated strain on deposited COL to facilitate the fiber growth.

Cell Dynamic Mechanics Regulates Large-spatial Isotropic Matrix Modeling with Computational Simulations

“…Early-stage cancer cell spheroids embedded into COL containing fibroblasts generated force for fibers alignment and CAFs induction[43]. Our work also showed that motile kidney epithelial cells (MDCK) can actively recruit soluble ECM from the medium to assemble base membrane or COL architectures in directing spherical or tubular tissue formations[44; 45]. The cell signals of integrin, RhoA, and actomyosin contraction show importance in cells-mediated ECM remodeling[4; 46].…”

Mechanical communication-induced cell directional migration and branching connections mediated by calcium channels, integrin β1 and N-cadherin

“…The property of nonlinear elastic extracellular matrix (ECM) from tissue can facilitate distant force transmission[20], and cell-generated stresses are capable of buckling COL filaments in ECM at large spatial extent[21; 22]. Our recent data has shown that motile cells can actively recruit environmental COL to assemble filaments for tissue-level assembly[23].…”