Understanding collective cell migration

Collective cell migration is key for development, cancer, and wound healing, and learning to control it will help us better grow and heal tissues. In all cases, collective migration involves large groups of cells coordinating their motion, such as occurs when cells work together to fill and heal an injury. Similarly, collective behaviors are essential to how cancers invade surrounding tissue or metastasize. We are developing a variety of precision tools to better perturb and understand these types of behaviors by combining microtissues, protein patterns, and biomaterials. At Left: We patterned circular ‘racetracks’ to study endothelial cell (blood vessels) leader-follower traffic dynamics.  

 

Bioelectric herding of collective cell migration

Given how important collective cell migration is to development, regeneration, and healing, we want to go beyond understanding it to trying to control it. If shepherds and dogs can herd sheep, we should be able to herd groups of cells in tissues and in the body if we can find the right signaling cues. To do this, we are tapping into the natural ability of cells to sense and follow DC electric fields–a process called galvanotaxis. More simply, when we get injured, there is a characteristic electrochemical response at the injury and cells can detect this and use it to help the healing process. Can we engineer this response to improve wound healing or how we grow tissues? To answer this question, we are developing new microstimulation tools that allow us to pattern specific electric field geometries on top of tissues and literally remote control their migration. We are now developing the next-gen bioelectric bioreactors to test the limits of this kind of control and to explore biomedical applications. At Right: kidney epithelial cells migrating back and forth in a Left-Right oscillating DC field.

Cell-Mimetic Biomaterials

Traditional biomaterials mimic the extra-cellular-matrix (ECM)–materials like collagen that cells attach to for support and structure. This means that we are very good at introducing materials to cells that look like natural ECM. However, there is a whole different class of cell-material interactions that we are only just beginning to explore–materials that mimic other cells rather than the ECM. In our work, we coat materials with proteins that cells use to recognize and adhere to each other (e.g. the cadherin proteins). In a sense, this biointerface emulates a ‘secret handshake’ with cells.  We are beginning to understand how to use this new kind of material in tissue engineering and biomedical applications and have ongoing collaborations involving skin, neural, and cardiac-mimetic materials and devices.
Below: Proof-of-concept of a 3D object that mimics epithelial cell-cell adhesion using a purified E-cadherin coating and a 3D geometry that resembles natural cell-cell junctions.