Pericyte actomyosin-mediated contraction at the cell-material interface can modulate the microvascular niche
Pericytes physically surround the capillary endothelium, contacting and communicating with associated vascular endothelial cells via cell-cell and cell-matrix contacts. Pericyte-endothelial cell interactions thus have the potential to modulate growth and function of the microvasculature. Here we emp...
| Main Authors: | , , , , , |
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| Other Authors: | , |
| Format: | Article |
| Language: | English |
| Published: |
Institute of Physics,
2011-06-15T15:44:18Z.
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| Subjects: | |
| Online Access: | Get fulltext |
| Summary: | Pericytes physically surround the capillary endothelium, contacting and communicating with associated vascular endothelial cells via cell-cell and cell-matrix contacts. Pericyte-endothelial cell interactions thus have the potential to modulate growth and function of the microvasculature. Here we employ the experimental finding that pericytes can buckle a freestanding, underlying membrane via actin-mediated contraction. Pericytes were cultured on deformable silicone substrata, and pericyte-generated wrinkles were imaged via both optical and atomic force microscopy (AFM). The local stiffness of subcellular domains both near and far from these wrinkles was investigated by using AFM-enabled nanoindentation to quantify effective elastic moduli. Substratum buckling contraction was quantified by the normalized change in length of initially flat regions of the substrata (corresponding to wrinkle contour lengths), and a model was used to relate local strain energies to pericyte contractile forces. The nature of pericyte-generated wrinkling and contractile protein-generated force transduction was further explored by the addition of pharmacological cytoskeletal inhibitors that affected contractile forces and the effective elastic moduli of pericyte domains. Actin-mediated forces are sufficient for pericytes to exert an average buckling contraction of 38% on the elastomeric substrata employed in these in vitro studies. Actomyosin-mediated contractile forces also act in vivo on the compliant environment of the microvasculature, including the basement membrane and other cells. Pericyte-generated substratum deformation can thus serve as a direct mechanical stimulus to adjacent vascular endothelial cells, and potentially alter the effective mechanical stiffness of nonlinear elastic extracellular matrices, to modulate pericyte-endothelial cell interactions that directly influence both physiologic and pathologic angiogenesis. National Science Foundation (U.S.) (CAREER Award) National Science Foundation (U.S.) (Chemical, Bioengineering, Environmental, and Transport Systems-0644846) National Institutes of Health (U.S.) (EY 19533) National Institutes of Health (U.S.) (EY 15125) |
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