Journal
LAB ON A CHIP
Volume 13, Issue 23, Pages 4599-4607Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3lc50802a
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Funding
- American Heart Association
- National Science Foundation [NSF-1159823]
- National Cancer Institute [T32-CA130840, F32-CA177756, U54-CA143868, CA101135]
- Kleberg Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1159823] Funding Source: National Science Foundation
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Cells migrate in vivo within three-dimensional (3D) extracellular matrices. Cells also migrate through 3D longitudinal channels formed between the connective tissue and the basement membrane of muscle, nerve, and epithelium. Although traction forces have been measured during 2D cell migration, no assay has been developed to probe forces during migration through confined microenvironments. We thus fabricated a novel microfluidic device consisting of deflectable PDMS microposts incorporated within microchannels of varying cross-sectional areas. Using NIH-3T3 fibroblasts and human osteosarcoma (HOS) cells as models, we found that the average traction forces per post decreased upon increasing confinement. Inhibition of myosin-II function by blebbistatin in HOS cells decreased traction forces in unconfined (wide) channels but failed to alter them in confined spaces. Myosin activation by calyculin A also failed to affect traction forces in confining channels but increased them in wide channels. These observations underlie the importance of the physical microenvironment in the regulation of cell migration and cellular traction forces.
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