Geometric control of capillary architecture via cell-matrix mechanical interactions

Jian Sun, Nima Jamilpour, Fei Yue Wang, Pak Kin Wong

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3273-3280
Number of pages8
JournalBiomaterials
Volume35
Issue number10
DOIs
StatePublished - Mar 2014

Keywords

  • Angiogenesis
  • Capillary morphogenesis
  • Cell-matrix interactions
  • Geometric constraints
  • Hydrogel

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint Dive into the research topics of 'Geometric control of capillary architecture via cell-matrix mechanical interactions'. Together they form a unique fingerprint.

  • Cite this