Geometric control of capillary architecture via cell-matrix mechanical interactions.
Capillary morphogenesis is a multistage, multicellular activity that plays a pivotal role in various developmental and pathological situations. In-depth understanding of the regulatory mechanism along with the capability of controlling the morphogenic process will have direct implications on tissue engineering and therapeutic angiogenesis. Extensive research has been devoted to elucidate the biochemical factors that regulate capillary morphogenesis. The roles of geometric confinement and cell-matrix mechanical interactions on the capillary architecture, nevertheless, remain largely unknown. Here, we show geometric control of endothelial network topology by creating physical confinements with microfabricated fences and wells. Decreasing the thickness of the matrix also results in comparable modulation of the network architecture, supporting the boundary effect is mediated mechanically. The regulatory role of cell-matrix mechanical interaction on the network topology is further supported by alternating the matrix stiffness by a cell-inert PEG-dextran hydrogel. Furthermore, reducing the cell traction force with a Rho-associated protein kinase inhibitor diminishes the boundary effect. Computational biomechanical analysis delineates the relationship between geometric confinement and cell-matrix mechanical interaction. Collectively, these results reveal a mechanoregulation scheme of endothelial cells to regulate the capillary network architecture via cell-matrix mechanical interactions.
Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, AZ 85721, USA.
Jian
J
Sun
Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, AZ 85721, USA.
Nima
N
Jamilpour
The Key Laboratory for Complex Systems and Intelligence Science, The Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Fei-Yue
FY
Wang
Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, AZ 85721, USA. Electronic address: pak@email.arizona.edu.
Pak Kin
PK
Wong
D002196:Capillaries / Q000033:anatomy & histology* / Q000254:growth & development; D003198:Computer Simulation; D004129:Dimethylpolysiloxanes; D006801:Humans; D020100:Hydrogels; D009024:Morphogenesis; D023822:Tissue Engineering
D004129:Dimethylpolysiloxanes; D020100:Hydrogels; C013830:baysilon
Angiogenesis; Capillary morphogenesis; Cell-matrix interactions; Geometric constraints; Hydrogel