CAREER: The Role of Surface Anisotropy in the Cellular Entry of Janus Particles

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CBET - 1554078PI: Yu, YanJanus particles are specialized particles whose surfaces have two distinct parts with different surface chemistry on each part. This two-faced feature makes Janus particles especially useful in novel biomedical applications, such as programmed drug delivery, provided the Janus particles can enter cells to carry out their functions. However, effects of the two-faced feature on cellular entry is not well understood. The goals of this CAREER project is to elucidate physical principles governing the entry of Janus particles into cells. Results from this project will provide guidance on how to use surface anisotropy to control the entry of synthetic particles into cells, which has the potential to transform the way multifunctional drug delivery particles are designed. The project will also promote interdisciplinary sciences and education at the interface of chemistry, engineering and biology. A Biomaterials Ambassadors outreach program will be established to bring interdisciplinary sciences to K-12 students and teachers in rural communities in Indiana. This new program will help address the urgent need of improving education in hard-to-reach areas. Visual methods of learning will also be developed to foster critical thinking in undergraduate education. This CAREER project will focus on ligand-guided cell entry of Janus microparticles. The hypothesis underlying the project is that the surface anisotropy of Janus particles alters the mechanism of cellular entry by changing the interplay between competing forces. To test this hypothesis, dynamics of Janus spheres will be measured with a new single-particle tracking method, which will reveal particle-cell interactions in multi-dimensions. Cellular dynamics, including membrane deformation and actin protrusion, will be measured with high-resolution fluorescence microscopy. The competition between surface anisotropy and shape in controlling the cellular entry pathways will also be investigated with non-spherical Janus particles. The results will establish a direct and quantitative connection between the particle-level anisotropies and the cell-level responses with unprecedented spatial and temporal resolution.