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

janus粒子是一种特殊的粒子，它的表面有两个不同的部分，每个部分的表面化学性质不同。这种双面特性使得Janus颗粒在新的生物医学应用中特别有用，例如程序化药物输送，只要Janus颗粒可以进入细胞执行其功能。然而，双面特征对细胞进入的影响尚不清楚。这个CAREER项目的目标是阐明控制Janus粒子进入细胞的物理原理。该项目的结果将为如何利用表面各向异性来控制合成颗粒进入细胞提供指导，这有可能改变多功能药物传递颗粒的设计方式。该项目还将促进化学、工程和生物交叉领域的跨学科科学和教育。将建立一个生物材料大使外展项目，向印第安纳州农村社区的K-12学生和教师介绍跨学科科学。这个新项目将帮助解决偏远地区改善教育的迫切需求。视觉学习方法也将在本科教育中发展，以培养批判性思维。这个CAREER项目将专注于配体引导Janus微粒进入细胞。该项目的假设基础是Janus粒子的表面各向异性通过改变竞争力之间的相互作用改变了进入细胞的机制。为了验证这一假设，Janus球的动力学将用一种新的单粒子跟踪方法来测量，这将揭示粒子-细胞在多维度上的相互作用。细胞动力学，包括膜变形和肌动蛋白突出，将用高分辨率荧光显微镜测量。表面各向异性和形状在控制细胞进入途径中的竞争也将在非球形Janus粒子中进行研究。该结果将以前所未有的空间和时间分辨率建立粒子水平各向异性与细胞水平响应之间的直接和定量联系。

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.