CAREER: Phase-separating Membrane Materials for Efficient and Specific Molecular Delivery to Cells

非技术性：这项由材料研究部生物材料项目授予德克萨斯大学奥斯汀分校的职业奖项是为药物输送系统开发生物材料。从消除癌症肿瘤到修复受损组织，医学经常依赖于我们将多种类型的治疗药物引导到患病细胞的能力，同时避免健康细胞暴露。该项目设计的生物材料能够准确识别病变细胞，并有效地向它们提供治疗药物。特别是，这项工作中开发的材料在识别疾病细胞表面的特定标记时，经历了从非交互状态到高度交互状态的戏剧性转变。这一策略将实现对疾病细胞的高度特异性治疗，提高药物治疗的能力和效率，同时减少副作用。此外，这项工作将创造新的机会，建立一系列简单的人造材料和系统，模仿活细胞感知和响应环境变化的能力。作为更广泛的影响活动的一部分，该项目计划通过邀请不同的新生群体为设计最小的“细胞状”系统贡献原创想法，增加少数族裔学生对STEM的参与。几名有希望的学生将被邀请在实验室进行试验，为他们提供一个独特的机会，通过将创造力与批判性思维相结合来解决现实世界的问题。通过在当地高中科学课堂上展示这些设计项目的结果，学生们将建立对他们在STEM中取得成功的能力的信心，同时激励下一代学生考虑STEM职业。技术：这项由材料研究部生物材料项目授予德克萨斯大学奥斯汀分校的职业奖项是开发用于药物输送系统的生物材料，以有效并特别地穿过细胞质膜运输大分子货物，如基因和蛋白质。在这个项目中，研究人员将模仿细胞相互识别的一种策略--将配体-受体结合到膜生物材料上，当它们识别靶细胞表面受体的阈值水平时，这些生物材料会出现阶段分离。该奖项由化学、生物工程、环境和运输系统部门的生物技术、生化和生物质工程项目共同资助。该项目将有效地解决大分子货物药物输送系统面临的一些挑战，特别是细胞内的挑战。该项目将使用合成和相分离脂质体设计和合成基于膜的生物材料。合成多聚体的设计将仔细调节其表面三元脂质混合物配体和融合蛋白的密度。在细胞-细胞识别和融合过程中，配体-受体的相互作用改变了局部的膜成分，导致细胞膜经历了高度局域化的相分离，极大地集中了配体和受体，加强了细胞与细胞的联系。在这些接触之后，当它们识别靶细胞表面受体的阈值水平时，这些膜生物材料相分离，驱动膜融合和将分子货物运送到细胞质。此外，这些材料还提供了新的工具，用于设计能够感知环境变化并对环境变化做出反应的“类细胞”系统。利用这一工具包，教育努力将集中在一门新课程上，这门课程将挑战非STEM专业的大一新生，让他们想出“简单的生物机器”的想法。这个独特的项目将邀请不同的学生群体分享科学创新的兴奋，而许多人仍在选择他们的学术专业和未来的职业，扩大我们校园对科学的参与。

Non-technical:This CAREER award by the Biomaterials program in the Division of Materials Research to University of Texas at Austin is to develop biomaterials for drug delivery system. From eliminating cancerous tumors to repairing damaged tissues, medicine frequently relies on our ability to direct multiple types of therapeutics to diseased cells, while sparing healthy cells from exposure. This project designs biomaterials that are capable of precisely recognizing diseased cells and efficiently delivering therapeutics to them. In particular, the materials developed in this work undergo a dramatic transformation from a non-interactive state to a highly interactive state when they recognize specific markers on the surfaces of diseased cells. This strategy will enable highly specific therapeutic delivery to diseased cells, increasing the capability and efficiency of pharmaceutical therapy while decreasing side effects. Furthermore, this work will create new opportunities to build a broad range of simple, man-made materials and systems that mimic the ability of living cells to sense and respond to changes in their environment. As part of the broader impact activities, this project plans to increase minority student participation in STEM, by inviting a diverse group of freshman students to contribute original ideas for the design of minimal 'cell-like' systems. Several students with promising ideas will be invited to try them out in the laboratory, providing them with a unique opportunity to solve real-world problems by combining creativity with critical thinking. By presenting the results of these design projects to local high school science classes, students will build confidence in their ability to succeed in STEM, while simultaneously inspiring the next generation of students to consider STEM careers.Technical:This CAREER award by the Biomaterials program in the Division of Materials Research to University of Texas at Austin is to develop biomaterials for drug delivery system to transport large macromolecular cargos such as genes and proteins efficiently and specifically across the cell's plasma membrane. In this project, the investigator will be mimicking a strategy used by cells to recognize one another -coupling of ligand-receptor binding to membrane biomaterials that phase separate when they recognize threshold levels of receptors on the surfaces of target cells. This award is cofunded by the Biotechnology, Biochemical, and Biomass Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. This project will be addressing some of the challenges facing the drug delivery system of large macromolecular cargos efficiently and specifically to inside of the cell. This project will design and synthesize membrane-based biomaterials using synthetic and phase separating liposomes. Synthetic polysomes will be designed with careful tuning the density of ternary lipid mixture ligands and fusion proteins on its surface. During cell-cell recognition and fusion, ligand-receptor interactions alter the local membrane composition, causing cellular membranes to undergo a highly localized phase separation that dramatically concentrates ligands and receptors, strengthening cell-cell contacts. Following these contacts, these membrane biomaterials phase separate when they recognize threshold levels of receptors on the surfaces of target cells, driving membrane fusion and delivery of molecular cargos to the cellular cytoplasm. Furthermore, these materials provide new tools for designing 'cell-like' systems that sense and respond to environmental changes. Drawing on this toolkit, educational efforts will center on a new course that will challenge freshman in non-STEM majors to come up with ideas for 'simple biological machines'. This unique project will invite a diverse group of students to share in the excitement of scientific innovation while many are still choosing their academic major and future career, broadening participation in science on our campus.