Toward Synthetic Neutrophils: De Novo Engineering of Chemotactic Artificial Cells

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Cell migration is important for many physiological processes and disease conditions, including angiogenesis, embryonic development, wound healing, immune defense, cancer metastasis, pathogen infection, and the establishment of neural circuits. Despite the biological importance of cell migration, relatively little is known about what is minimally required to allow a cell to move. The goals of this project are to use an artificial cell-like system to define the minimal requirements for cell migration and ultimately to be able to control the movements of cells for applications in medicine and biotechnology. Based on the interdisciplinary nature of their research theme, the team will create unique opportunities to promote STEM research and education for undergraduate and graduate students. In parallel, they will expand an existing course on synthetic biology into a new course, “Synthetic and Computational Cell Biology”. This course will connect diverse communities and raise their awareness of the power of this interdisciplinary subject in dissecting basic principles of complex biology. Chemotaxis plays a fundamental role throughout biology ranging from embryonic development to immune response. Despite its physiological significance and intense research over last decades, there is still a lack of full understanding of the molecular mechanisms underlying cell migratory behaviors. The primary challenge is rooted in the profound complexity of two signaling modalities: the biochemical reactions that involve signal transduction and the biomechanical actuations that induce membrane deformations. By taking a bottom-up approach, the investigators recently generated an artificial cell made of giant unilamellar vesicles, which could undergo symmetry breaking upon addition of an external chemical stimulus. This behavior is characteristic of cell polarization, one of the key events observed during native chemotaxis. Built on this experimental system and guided by theoretical modeling, the team aims to identify and assemble a minimal set of biomolecules inside the vesicles to generate desired types of membrane deformations as well as motility. 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.