Independent regulation of tumor cell migration by matrix stiffness and confinement

Tumor invasion and metastasis are strongly regulated by biophysical interactions between tumor cells and the extracellular matrix (ECM). While the influence of ECM stiffness on cell migration, adhesion, and contractility has been extensively studied in 2D culture, extension of this concept to 3D cultures that more closely resemble tissue has proven challenging, because perturbations that change matrix stiffness often concurrently change cellular confinement. This coupling is particularly problematic given that matrix-imposed steric barriers can regulate invasion speed independent of mechanics. Here we introduce a matrix platform based on microfabrication of channels of defined wall stiffness and geometry that…

• NS
  National Science Foundation

  Awards: 1105539, CMMI 1105539
• NI
  National Institutes of Health

  Awards: CMMI 1105539, 1U54CA143836, 1DP2OD004213
• DO
  Division of Civil, Mechanical and Manufacturing Innovation