Journal
BIOMATERIALS
Volume 33, Issue 16, Pages 4157-4165Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.02.029
Keywords
Collagen; Microstructure; ECM (extracellular matrix); Cell morphology; Cell spreading; Confocal microscopy
Funding
- Cornell Center on the Microenvironment & Metastasis from the National Cancer Institute [U54CA143876]
- National Science Foundation
- Howard Hughes Medical Institute
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Fibrillar collagen gels, which are used extensively in vitro to study tumor-microenvironment interactions, are composed of a cell-instructive network of interconnected fibers and pores whose organization is sensitive to polymerization conditions such as bulk concentration, pH, and temperature. Using confocal reflectance microscopy and image autocorrelation analysis to quantitatively assess gel microarchitecture, we show that additional polymerization parameters including culture media formulation and gel thickness significantly affect the dimensions and organization of fibers and pores in collagen gels. These findings enabled the development of a three-dimensional culture system in which cell-scale gel microarchitecture was decoupled from bulk gel collagen concentration. Interestingly, morphology and migration characteristics of embedded MDA-MB-231 cells were sensitive to gel microarchitecture independently of collagen gel concentration. Cells adopted a polarized, motile phenotype in gels with larger fibers and pores and a rounded or stellate, less motile phenotype in gels with small fibers and pores regardless of bulk gel density. Conversely, cell proliferation was sensitive to gel concentration but not microarchitecture. These results indicate that cell-scale gel microarchitecture may trump bulk-scale gel density in controlling specific cell behaviors, underscoring the biophysical role of gel microarchitecture in influencing cell behavior. (c) 2012 Elsevier Ltd. All rights reserved.
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