The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro

A. L. Sieminski, R. P. Hebbel, K. J. Gooch

Research output: Contribution to journalArticlepeer-review

220 Scopus citations

Abstract

When suspended in collagen gels, endothelial cells elongate and form capillary-like networks containing lumens. Human blood outgrowth endothelial cells (HBOEC) suspended in relatively rigid 3 mg/ml floating collagen gels, formed in vivo-like, thin, branched multi-cellular structures with small, thick-walled lumens, while human umbilical vein endothelial cells (HUVEC) formed fewer multi-cellular structures, had a spread appearance, and had larger lumens. HBOEC exert more traction on collagen gels than HUVEC as evidenced by greater contraction of floating gels. When the stiffness of floating gels was decreased by decreasing the collagen concentration from 3 to 1.5 mg/ml, HUVEC contracted gels more and formed thin, multi-cellular structures with small lumens, similar in appearance to HBOEC in floating 3 mg/ml gels. In contrast to floating gels, traction forces exerted by cells in mechanically constrained gels encounter considerable resistance. In constrained collagen gels (3 mg/ml), both cell types appeared spread, formed structures with fewer cells, had larger, thinner-walled lumens than in floating gels, and showed prominent actin stress fibers, not seen in floating gels. These results suggest that the relative magnitudes of cellular force generation and apparent matrix stiffness modulate capillary morphogenesis in vitro and that this balance may play a role in regulating angiogenesis in vivo.

Original languageEnglish (US)
Pages (from-to)574-584
Number of pages11
JournalExperimental Cell Research
Volume297
Issue number2
DOIs
StatePublished - Jul 15 2004

Keywords

  • Capillary morphogenesis
  • Cell traction
  • In vitro angiogenesis
  • Matrix stiffness

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