We have been investigating the responses of cell migration to physical signals such as stiffness, forces, geometry, and 3D topography. Since the formation of most tissues involves the migration of different cell types to specific locations, the knowledge is important to tissue engineering and repair. In addition to properties like speed, persistence, and directionality, we are examining the initiation of cell migration known as symmetry breaking, and the migration of cell collectives, where the cross-talks between cell-cell interactions and cell migration can lead to the formation of complex structures and macroscopic shapes.

Cells in many parts of the body, including blood vessels and lungs, experience cyclic mechanical forces, which are known to cause profound responses.  For example, many cell types show reorientation perpendicular to the direction of cyclic forces, but the mechanism is unclear.  We have designed a novel approach for recording the distinct responses during the stretching and relaxation phases of a stretching cycle, under the hypothesis that reorientation is driven by differential retraction or extension along perpendicular directions, possibly in response to stretching and relaxation respectively.  In addition, we are testing the hypothesis that the combined responses of cell orientation, cell migration, and cell-cell adhesion may cause cell colonies to undergo rearrangement and morphogenesis-like events.

Traction force microscopy, as a fundamental tool in mechanobiology, maps the mechanical stress a cell applies to a surface. Cells are plated on elastic substrates embedded with fluorescent microbeads as markers.  Linear elastic theory is then used for calculating the distribution of stress based on strains detected with the beads.  However, since its introduction more than 20 years ago , traction force microscopy suffers from limited resolution and accuracy due its nature as an ill-posed mathematical problem.  To improve the performance of traction force microscopy, we are now using machine learning, trained with large datasets generated by a mathematical model , as a novel approach to overcome the challenge , In addition, since traction force microscopy requires accurate knowledge of the elasticity of the detection substrate, we have used 3D printing to fabricate a rheometer designed to optimize stiffness measurements of soft hydrogels used in traction force microscopy and other mechanobiological studies.

To expand the use of polyacrylamide, which has many favoriable chemical and physical properties for a wide range of biomedical applications, we have developed a method to generate complex structures using stereolithography 3D printing .  The approach is being used to generate micropatterned surfaces and 3D environments as tools for basic mechanobiology.  An initial example is a substrate with precisely micropatterend stiffness, which we have used for studying durotaxis and stiffness-driven segregation of cell collectives.  We are also developing devices with complex compartments and channels divided by water permeable polyacrylamide partitions, which may serve as prototypic artificial organs or chemical reactors.