title: Effect of Static Pre-stretch Induced Surface Anisotropy on Orientation of Mesenchymal Stem Cells.
abstract: Mechanical cues in the cellular environment play important roles in guiding various cell behaviors, such as cell alignment, migration, and differentiation. Previous studies investigated mechanical stretch guided cell alignment pre-dominantly with cyclic stretching whereby an external force is applied to stretch the substrate dynamically (i.e., cyclically) while the cells are attached onto the substrate. In contrast, we created a static pre-stretched anisotropic surface in which the cells were seeded subsequent to stretching the substrate. We hypothesized that the cell senses the physical environment through a more active mechanism, namely, even without external forces the cell can actively apply traction and sense an increased stiffness in the stretched direction and align in that direction. To test our hypothesis, we quantified the extent of pre-stretch induced anisotropy by employing the theory of small deformation superimposed on large and predicted the effective stiffness in the stretch direction as well as its perpendicular direction. We showed mesenchymal stem cells (MSC) aligned in the pre-stretched direction, and the cell alignment and morphology were dependent on the pre-stretch magnitude. In addition, the pre-stretched surface demonstrated an ability to promote early myoblast differentiation of the MSC. This study is the first report on MSC alignment on a statically pre-stretched surface. The cell orientation induced by the pre-stretch induced anisotropy could provide insight into tissue engineering applications involving cells that alignedin vivoin the absence of dynamic mechanical stimuli.
authors.affiliation: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Mechanical Engineering, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: S
authors.initials: S
authors.lastname: Baek
authors.affiliation: Department of Mechanical Engineering, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: E
authors.initials: E
authors.lastname: Vasko
authors.affiliation: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pyne
authors.affiliation: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chan
keywords: Anisotropy, Orientation; Mechano-sensing; Mesenchymal stem cells; Static pre-stretch