CAREER: The nanoscale dynamics of molecular sorting, membrane curvature, and endocytosis

非技术性：这个由材料研究部的生物材料项目授予韦恩州立大学的职业奖项是为了支持专注于纳米级膜工艺的研究和教育努力。生物膜是一种复杂的、动态的二维流体结构，负责结合、内化和运输材料。目前对膜过程的了解还不够充分，这种缺乏深入的知识限制了生物医学在各种神经学、免疫学和代谢条件下的进展。了解和解决潜在的膜过程将指导新型膜材料在电池、长期食品保鲜、脂质体货物(药物、DNA、RNA等)中的潜在应用。无内含体摄取的分娩等。此外，该奖项的教育影响将是对技术熟练劳动力的培训，这些努力将与密歇根科学中心协调。该奖项将支持针对下一代科学标准的实践教育计划的开发和实施，这些活动预计每年将影响到当地大量的K-12学生。技术：该职业奖支持开发和使用纳米光学方法来测量膜曲率和功能的分子尺度原因和影响。利用偏振定位显微镜，能够同时测量动态膜曲率和分子结构的超分辨率光学技术，将开展以下研究：1)量化纳米膜曲率与脂质相分离的相互作用；2)解决曲率传感和脂相偏好对磷脂酰肌醇磷酸盐分选的贡献；以及3)观察笼蛋白和小窝蛋白非依赖性内吞作用周围的纳米膜组织结构。膜的功能需要了解膜的许多成分，包括膜的横向组成变化、膜物理性质的局部变化，如厚度、弯曲、刚性、张力、曲率和流动性。通过了解调控膜功能的基本物理原理之间的相互依存关系，该项目将为开发新型仿生膜和在科学技术领域的应用奠定基础。这项研究还将解决以前无法验证的关于启动受体非依赖性内吞作用的机制的假说。这些研究的结果将指导基础科学家了解纳米生物学的机制，以及旨在更好地控制膜过程和功能的应用科学家，包括对高通量膜、脂质体药物靶向和纳升化学应用至关重要的膜特性之间的相互作用。此外，该奖项将支持纳米技术的发展，提高对纳米生物学的理解，并通过培训学生来传播这些进步。拟议的与密歇根科学中心协调的教育和培训活动预计将影响到大量K-12学生，为他们接受STEM高等教育和拥有技术熟练的劳动力做好准备。经济和社会将受益于拟议中的高科技劳动力培训、提高科学素养、新的生物学见解以及该奖项所带来的技术进步。

Nontechnical: This CAREER award by the Biomaterials program in the Division of Materials Research to Wayne State University is to support the research and educational efforts focused on nanoscale membrane processes. Biological membranes are complex and dynamic two-dimensional fluid structures that are responsible for binding, internalizing and transporting materials. Membrane processes are inadequately understood at present, and this lack of in depth knowledge is limiting biomedical advancement in diverse neurological, immunological, and metabolic conditions. Developing an understanding and resolving the underlying membrane processes would guide the development of novel membrane like materials for potential applications in battery, long term food preservation, liposome-based cargo (drug, DNA, RNA, etc.) delivery without endosome uptake among others. Further, the educational impact of this award will be in the training of a technically skilled workforce, and these efforts will be coordinated with the Michigan Science Center. This award will support the development and implementation of a hands-on educational program to address the Next-Generation Science Standards, and these activities are expected to impact a large number of local K-12 students annually. Technical: This CAREER award supports the development and use of nanoscopic optical methods to measure the molecular-scale causes and effects of membrane curvature and functions. Using polarized localization microscopy, a super-resolution optical technique developed by the PI that is capable of simultaneously measuring dynamic membrane curvature and molecular organization, the following studies will be carried out to: 1) quantify the interplay of nanoscale membrane curvature with lipid phase separation; 2) resolve the contributions of curvature sensing and lipid phase preference on the sorting of phosphoinositide phosphates; and 3) observe the nanoscale membrane organization surrounding clathrin- and caveolin-independent endocytosis. Membrane functions require an understanding of many components of membranes including lateral composition variation, local variations in membrane physical properties such as thickness, bending, rigidity, tension, curvature, and fluidity. By understanding the interdependence of fundamental physical principles that regulate membrane functions, this project would create a foundational understanding in developing novel biomimetic membranes and applications in scientific and technological fields. This research will also address previously untestable hypotheses regarding the mechanisms initiating receptor-independent endocytosis. The results from these studies will guide both basic scientists to understand mechanisms in nano-biology, and applied scientists aiming to better control membrane processes and functions including the interplay between membrane properties that are critical for high-throughput membranes, liposome-based drug targeting, and nanoliter chemistry applications. Additionally, this award will support the development of nanoscopic methods, improved understandings of nanoscale biology, and dissemination of these advancements through the training of students. The proposed educational and training activities in coordination with the Michigan Science Center are expected to impact a large number of K-12 students in preparing them for higher education in STEM and a technically skilled workforce. The economy and society will benefit from the proposed training of a high-tech workforce, improved scientific literacy, new biological insights, and technological advances made possible by this award.