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| Content Provider | Royal Society of Chemistry (RSC) |
|---|---|
| Author | Weidling, John W. Digman, Michelle A. Kniazeva, Ekaterina Botvinick, Elliot L. Gratton, Enrico Putnam, Andrew J. Singh, Rahul |
| Copyright Year | 2012 |
| Abstract | Reciprocal mechanical interactions between cells and the extracellular matrix (ECM) are thought to play important instructive roles in branching morphogenesis. However, most studies to date have failed to characterize these interactions on a length scale relevant to cells, especially in three-dimensional (3D) matrices. Here we utilized two complementary methods, spatio-temporal image correlation spectroscopy (STICS) and laser optical tweezers-based active microrheology (AMR), to quantify endothelial cell (EC)-mediated deformations of individual ECM elements and the local ECM mechanical properties, respectively, during the process of capillary morphogenesis in a 3D cell culture model. In experiments in which the ECM density was systematically varied, STICS revealed that the rate at which ECs deformed individual ECM fibers on the microscale positively correlated with capillary sprouting on the macroscale. ECs expressing constitutively active V14-RhoA displaced individual matrix fibers at significantly faster rates and displayed enhanced capillary sprouting relative to wild-type cells, while those expressing dominant-negative N19-RhoA behaved in an opposite fashion. In parallel, AMR revealed a local stiffening of the ECM proximal to the tips of sprouting ECs. By quantifying the dynamic physical properties of the cell-ECM interface in both space and time, we identified a correlation linking ECM deformation rates and local ECM stiffening at the microscale with capillary morphogenesis at the macroscale. |
| Starting Page | 431 |
| Ending Page | 439 |
| Page Count | 9 |
| File Format | HTM / HTML PDF |
| ISSN | 17579694 |
| Volume Number | 4 |
| Issue Number | 4 |
| Journal | Integrative Biology |
| DOI | 10.1039/c2ib00120a |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Access Restriction | Open |
| Subject Keyword | AMR EC Extracellular matrix Morphogenesis Three-dimensional space Two-dimensional nuclear magnetic resonance spectroscopy Laser Microrheology Endothelium 3D cell culture RHOA N postcode area |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry Biophysics |
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