Spatially Patterned Nano/Microparticles to Traverse Biological Barriers

非技术：该奖项由材料研究部生物材料项目颁发，旨在创造和研究新型多功能颗粒，这些颗粒模拟细菌过程，用于药物输送等有益目的。这种生物材料是基于一种新创建的Janus粒子形式，它以空间上不同的方式显示粒子上的生物配体，例如具有左右半球。由于颗粒配体是聚集和极化的，因此颗粒可以利用高效的生物反应进入细胞并在细胞内转运。将研究颗粒与血脑屏障模型的相互作用，以了解颗粒递送到大脑的效率。该项目将为研究生和本科生提供跨学科的生物材料、微技术和神经科学方面的培训机会。研究活动还将通过在亚特兰大公立高中的外展活动，促进在尖端科学技术方面招募和指导不同的学生。技术方面：能够主动穿越生物屏障（如血脑屏障）的粒子将对各种基础科学和应用目的非常有益。穿越生物屏障是一些病原体的常规表现。例如，单核增生李斯特菌可以不对称地表达特定的蛋白质，有效地内化到细胞中，逃离吞噬体，并通过有核肌动蛋白聚合在细胞质内激活以逃离细胞。然而，设计能够完成这些任务的生物材料是一个挑战。本研究旨在创造新的多功能颗粒，模拟致病机制进入上皮细胞层，并在细胞内主动运输，从基侧退出。Janus颗粒将被设计成一种新型的多功能，地形不同的颗粒，可以自主地穿过上皮屏障。这些颗粒将通过微图案技术制造出来，在颗粒表面产生化学上不同的区域，效应蛋白与这些区域相连，介导胞吞作用的每个步骤。研究人员假设，通过地形分离的高密度效应配体将设计具有生物有机体特有的有效和协调的配体介导过程的颗粒。将研究颗粒与血脑屏障模型的相互作用，以了解颗粒输送到大脑和大脑内部的效率。该计划将有助于激励来自不同学科和背景的研究生和本科生研究微制造技术如何利用仿生效应来创造新的仿生材料，以广泛影响生物科学。此外，该计划还将为工程师和科学家设计多功能粒子开发新的课程，这将进一步包括招募高中生和教师为研究做出贡献。

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.