Guiding cell migration in 3D: a collagen matrix with graded directional stiffness

Cell Motil Cytoskeleton. 2009 Mar;66(3):121-8. doi: 10.1002/cm.20331.


While matrix stiffness has been implicated in cell adhesion and migration, most studies have focused on the effects of substrate stiffness in 2D. The present work describes a novel continuous stiffness gradient model for studying such processes in 3D. Wedge-shaped collagen scaffolds were compressed to produce sheets of a desired (0.1 mm) uniform thickness, but with increasing collagen density along the length of the sheet. Dynamic mechanical analysis, carried out on 1 mm wide strips obtained from the two ends and the middle of each sheet, showed that the elastic modulus increased from 1057 +/- 487 kPa to 2305 +/- 693 kPa at the soft and stiff end respectively and was 1835 +/- 31 kPa in the middle. In constructs seeded with agarose marker beads prior to compression, mean agarose bead density rose from 10 +/- 1 to 71 +/- 12 at the soft and stiff end respectively and was 19 +/- 5 in the middle, indicating successful engineering of a density gradient corresponding to the measured stiffness gradient. Growth-arrested human dermal fibroblasts, initially seeded evenly within such constructs, accumulated preferentially towards the stiff part of the gradient after 3 and 6 days in culture. Durotactic migration was significant after 6 days. This model provides a new means for studying cellular mechanotaxis and patterning cells which is controllable, biomimetic and in 3D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Culture Techniques
  • Cell Movement / physiology*
  • Cells, Cultured
  • Collagen / metabolism*
  • Dermis / cytology
  • Extracellular Matrix / metabolism*
  • Fibroblasts / physiology*
  • Humans
  • Models, Biological*
  • Stress, Mechanical*


  • Collagen