NSF Award
2412942
Surprisingly, when tissues like the skin or cornea are wounded, our bodies immediately respond by creating a natural electric field pointing toward the wound center. These fields have nothing to do with the brain or nervous system. Instead, cells can actually use the electric field to navigate, leading them to the wound site (“electrotaxis” or “galvanotaxis”). Controlling this electrical signal is thought to be able to improve our own ability to heal. However, developing next-generation ‘electroceutical’ tools requires us to better understand what cells are doing when following this signal – how do they detect an electric field, and what limits their ability to sense it? Understanding this requires a focus on the interaction between biological cell motility and the physical forces applied to molecules on the cell’s surface. Currently, most of the data in this field suggest that cells follow electric fields because charged sensor molecules are redistributed on the cell’s surface. However, these molecules are so small that the electrical signal will be competing with fluctuating thermal forces (Brownian motion). This competition could affect how accurately cell can respond to the electrical signals and understanding it could lead to better ways to deliver electrical signals to improve cell responses. This project will study how these physical factors limit the accuracy of how both individual cells and groups of cells follow fields. The research is a collaboration between the Camley group, who model how groups of cells respond to chemical cues and have recently developed a biophysical model for single-cell galvanotaxis, and the Cohen group, who are experts in engineering and controlling electrotaxis at the tissue scale. This project will support the development of computational models that include the motion of sensor molecules on the cell’s surface in response to electric fields, the crawling of the cell, and the ways in which cells can influence the electric fields around them. The project will then involve testing these models using experiments with single cells, small numbers of cells, and tissues, and use this data to refine the models. The Broader Impacts of this work include a better understanding of these processes essential to wound healing, as well as developing tools to help guide individual cells or cell sheets—all of which brings us closer to new bioelectric technologies for healing. In addition, this project will support training of scientists in broad communication, outreach, and storytelling through an expansion of Cohen’s ‘Lab Tales’ storytelling training workshop where trainees learn science history and storytelling through a week of hands-on instruction. <br/><br/>In more detail, this award will aim to answer three broad questions. First: how does a cell’s shape affect its ability to sense a field? Many single eukaryotic cells stretch perpendicular to an applied electric field. Why? Does it benefit them? To answer, the project will study how the ‘front’ and ‘back’ of a cell reorients when exposed to an electric field, and how this depends on cell shape and orientation. The project will control cell shape by using adhesive micropatterns, allowing for quantitative comparison with theory. Second: Do cells interact while galvanotaxing? Cells, by their presence on the substrate, will alter the local electric field. Can pairs of cells interact through the electric field, with one cell causing the other to reorient? Third: Can groups of cells improve their accuracy by aligning? Many cell types develop so-called “nematic” alignment, where cells’ long axes align with each other – this also includes keratinocytes following electrical fields. How does this affect the group’s ability to respond to signals?<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
