Guiding cell migration in 3D: A collagen matrix with graded directional stiffness
- 23 January 2009
- journal article
- research article
- Published by Wiley in Cell Motility
- Vol. 66 (3), 121-128
- https://doi.org/10.1002/cm.20331
Abstract
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. Cell Motil. Cytoskeleton 66: 121–128, 2009.Keywords
This publication has 31 references indexed in Scilit:
- Engineering Functional Collagen Scaffolds: Cyclical Loading Increases Material Strength and Fibril AggregationAdvanced Functional Materials, 2007
- Collagen stiffness regulates cellular contraction and matrix remodeling gene expressionJournal of Biomedical Materials Research Part A, 2007
- Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substratesProceedings of the National Academy of Sciences of the United States of America, 2007
- Formation and Function of the Myofibroblast during Tissue RepairJournal of Investigative Dermatology, 2007
- Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic propertiesBiomaterials, 2006
- A novel “sandwich” assay for quantifying chemo-regulated cell migration within 3-dimensional matrices: Wound healing cytokines exhibit distinct motogenic activities compared to the transmembrane assayCell Motility, 2006
- Nested collagen matrices: A new model to study migration of human fibroblast populations in three dimensionsExperimental Cell Research, 2006
- Effects of collagen density on cardiac fibroblast behavior and gene expressionJournal of Cellular Physiology, 2003
- Encounters in SpaceScience, 2001
- Tumor cell haptotaxis on covalently immobilized linear and exponential gradients of a cell adhesion peptideDevelopmental Biology, 1989