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

职业生涯：表面各向异性在 Janus 粒子进入细胞中的作用

• 批准号: 1554078
• 负责人: Yan Yu
• 金额: $ 50万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-15 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1554078&HistoricalAwards=false
• 关键词: CAREER; Role; Surface; Anisotropy; Cellular

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.

CBET - 1554078PI：Yu，YanJanus 颗粒是一种特殊颗粒，其表面有两个不同的部分，每个部分的表面化学性质不同。 这种双面特征使得 Janus 粒子在新颖的生物医学应用中特别有用，例如程序化药物输送，前提是 Janus 粒子可以进入细胞来执行其功能。 然而，双面特征对细胞进入的影响尚不清楚。 这个职业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输送颗粒的设计方式。该项目还将促进化学、工程和生物学交叉领域的跨学科科学和教育。将建立生物材料大使推广计划，为印第安纳州农村社区的 K-12 学生和教师带来跨学科科学。 这项新计划将有助于解决改善偏远地区教育的迫切需求。还将开发视觉学习方法，以培养本科教育中的批判性思维。该职业项目将重点关注配体引导的 Janus 微粒进入细胞。该项目的假设是，Janus 粒子的表面各向异性通过改变竞争力之间的相互作用来改变细胞进入的机制。为了验证这一假设，将使用一种新的单粒子跟踪方法来测量 Janus 球体的动力学，该方法将揭示多维的粒子-细胞相互作用。细胞动力学，包括膜变形和肌动蛋白突出，将通过高分辨率荧光显微镜进行测量。表面各向异性和形状之间在控制细胞进入途径方面的竞争也将用非球形 Janus 颗粒进行研究。结果将以前所未有的空间和时间分辨率在粒子级各向异性和细胞级响应之间建立直接和定量的联系。

项目成果

Anisotropic presentation of ligands on cargos modulates degradative function of phagosomes

货物上配体的各向异性呈现调节吞噬体的降解功能

• DOI: 10.1016/j.bpr.2021.100041
• 发表时间: 2022
• 期刊: Biophysical Reports
• 作者: Jiao, Mengchi;Li, Wenqian;Yu, Yanqi;Yu, Yan
• 通讯作者: Yu, Yan