title: Guiding cell migration in 3D: a collagen matrix with graded directional stiffness.
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.
authors.affiliation: University College London, Tissue Repair and Engineering Centre, Institute of Orthopaedics, United Kingdom.
authors.forename: Ektoras
authors.initials: E
authors.lastname: Hadjipanayi
authors.forename: Vivek
authors.initials: V
authors.lastname: Mudera
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brown
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D020405:Dermis / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D013314:Stress, Mechanical
chemical_list: D003094:Collagen