Journal
FASEB JOURNAL
Volume 33, Issue 10, Pages 10618-10632Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201900131R
Keywords
persistent cell migration; 2D migration; 3D migration; nucleus geometry; cell-ECM interaction
Categories
Funding
- Institute of Critical Technologies and Sciences (ICTAS) at Virginia Tech
- National Science Foundation (NSF) [1437101, 1462916]
- NSF [1454226]
- U.S. National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) [P20GM125503]
- U.S. NIH National Cancer Institute (NCI) [R01CA214511-01A1]
- American Thyroid Association Thyroid Cancer Survivors Association (ThyCa)
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1454226] Funding Source: National Science Foundation
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1462916, 1437101] Funding Source: National Science Foundation
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Biomechanical cues within tissue microenvironments are critical for maintaining homeostasis, and their disruption can contribute to malignant transformation and metastasis. Once transformed, metastatic cancer cells can migrate persistently by adapting (plasticity) to changes in the local fibrous extracellular matrix, and current strategies to recapitulate persistent migration rely exclusively on the use of aligned geometries. Here, the controlled interfiber spacing in suspended crosshatch networks of nanofibers induces cells to exhibit plasticity in migratory behavior (persistent and random) and the associated cytoskeletal arrangement. At dense spacing (3 and 6 mu m), unexpectedly, elongated cells migrate persistently (in 1 dimension) at high speeds in 3-dimensional shapes with thick nuclei, and short focal adhesion cluster (FAC) lengths. With increased spacing (18 and 36 mu m), cells attain 2-dimensional morphologies, have flattened nuclei and longer FACs, and migrate randomly by rapidly detaching their trailing edges that strain the nuclei by similar to 35%. At 54-mu m spacing, kite-shaped cells become near stationary. Poorly developed filamentous actin stress fibers are found only in cells on 3-mu m networks. Gene-expression profiling shows a decrease in transcriptional potential and a differential up-regulation of metabolic pathways. The consistency in observed phenotypes across cell lines supports using this platform to dissect hallmarks of plasticity in migration in vitro.-Jana, A., Nookaew, I., Singh, J., Behkam, B., Franco, A. T., Nain, A. S. Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response.
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