title: Vascular smooth muscle cell durotaxis depends on extracellular matrix composition.
abstract: Mechanical compliance has been demonstrated to be a key determinant of cell behavior, directing processes such as spreading, migration, and differentiation. Durotaxis, directional migration from softer to more stiff regions of a substrate, has been observed for a variety of cell types. Recent stiffness mapping experiments have shown that local changes in tissue stiffness in disease are often accompanied by an altered ECM composition in vivo. However, the importance of ECM composition in durotaxis has not yet been explored. To address this question, we have developed and characterized a polyacrylamide hydrogel culture platform featuring highly tunable gradients in mechanical stiffness. This feature, together with the ability to control ECM composition, allows us to isolate the effects of mechanical and biological signals on cell migratory behavior. Using this system, we have tracked vascular smooth muscle cell migration in vitro and quantitatively analyzed differences in cell migration as a function of ECM composition. Our results show that vascular smooth muscle cells undergo durotaxis on mechanical gradients coated with fibronectin but not on those coated with laminin. These findings indicate that the composition of the adhesion ligand is a critical determinant of a cell's migratory response to mechanical gradients.
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hartman
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215.
authors.forename: Brett C
authors.initials: BC
authors.lastname: Isenberg
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215.
authors.forename: Samantha G
authors.initials: SG
authors.lastname: Chua
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215 jywong@bu.edu.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Wong
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D058948:Cell Tracking / Q000379:methods; D004548:Elasticity; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007797:Laminin / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D000180:Acrylic Resins; D005353:Fibronectins; D007797:Laminin; D008024:Ligands; C016680:polyacrylamide gels; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: cell migration; durotaxis; extracellular matrix; polyacrylamide