Patterning Cellular Alignment through Stretching Hydrogels with Programmable Strain Gradients

The graded mechanical properties (e.g., stiffness and stress/strain) of excellular matrix play an important role in guiding cellular alignment, as vital in tissue reconstruction with proper functions. Though various methods have been developed to engineer a graded mechanical environment to study its effect on cellular behaviors, most of them failed to distinguish stiffness effect from stress/strain effect during mechanical loading. Here, we construct a mechanical environment with programmable strain gradients by using a hydrogel of a linear elastic property. When seeding cells on such hydrogels, we demonstrate that the pattern of cellular alignment can be rather precisely tailored by substrate strains. The experiment is in consistency with a theoritical prediction when assuming that focal adhesions (FAs) would drive a cell to reorient to the directions where they are most stable. A fundamental theory has also been developed and is excellent in agreement with the complete temporal alignment of cells. This work not only provides important insights into the cellular response to the local mechanical microenvironment but can also be utilized to engineer patterned cellular alignment that can be critical in tissue remodeling and regenerative medicine applications.