Spatially Patterned Nano/Microparticles to Traverse Biological Barriers

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Non-Technical: This award by the Biomaterials program in the Division of Materials Research is to create and study novel multifunctional particles which mimic bacterial processes for beneficial purposes such as drug delivery. The biomaterial is based upon a newly created form of Janus particle, which displays biological ligands on a particle in a spatially distinct manner, for example with a right and left hemisphere. Since the particle ligands are clustered and polarized, highly effective biological reactions can be harnessed by the particle to enter cells and translocate within cells. Interactions of the particles with a model of the blood brain barrier will be studied to understand the efficiency of particle delivery to the brain. This project will provide interdisciplinary training opportunities to graduate and undergraduate students on biomaterials, microtechnology, and neuroscience. The research activities will also promote the recruitment and mentoring of diverse students in cutting-edge scientific techniques through outreach in the Atlanta public high schools.Technical: Particles that can actively traverse biological barriers, such as the blood-brain barrier, would be highly beneficial for a variety of basic science and applied purposes. Traversing biological barriers is routinely demonstrated by some pathogens. For example, the bacterium Listeria monocytogenes can asymmetrically express specific proteins to efficiently internalize into cells, escape a phagosome, and actuate within the cell cytosol via nucleated actin polymerization to escape the cell. However, designing biomaterials that can accomplish these tasks is a challenge. This study aims to create new, multifunctional particles which mimic pathogenic mechanisms to enter an epithelial cell layer and actively transport within the cell to exit on the basal side. Janus particles will be designed as a new class of multifunctional, topographically distinct particles that can autonomously transverse an epithelial barrier. These particles will be created with micropatterning technologies to produce chemically-distinct regions on the particle surface to which effector proteins are linked to mediate each step of transcytosis. The investigators hypothesize that high density of effector ligands through topographic separation will engineer particles with potent and coordinated ligand-mediated processes characteristically achieved by biological organisms. Interactions of the particles with a model of the blood brain barrier will be studied to understand the efficiency of particle delivery to and within the brain. The proposed program will help inspire graduate and undergraduate students from diverse disciplines and backgrounds to study how microfabrication technologies can harness bio-inspired effectors to create new biomimetic materials to widely impact the biosciences. Additionally the program will develop new curriculum for engineers and scientists to design multifunctional particles, which will further include the recruiting of high school students and teachers to contribute to research studies.