IDBR: Development of a Spectroscopic Instrument for the Study of Vibrational Relaxation and Local Motion in Biomolecular Systems

这项提议是为了建造一种仪器，它将提供以前无法获得的关于质膜、仿生结构和捕光蛋白质的组织和动力学的信息。脂质双层和捕光蛋白中的能量耗散还不是很清楚，但被认为是这两类不同生物分子系统的中介功能。这个项目解决的一个广泛的生物学问题是形成脂筏结构的基本分子基础，以及为什么这种结构随着双层成分的浓度和特性而变化。要了解脂筏组织的分子结构基础，需要能够测量脂双层成分的粘弹性和分子间相互作用。拟议的仪器将允许测量生物分子系统中的分子运动和热能流动。这个项目需要设计、建造和表征一个仪器，该仪器将应用受激发射光谱来研究生物膜和蛋白质的结构和动力学。该仪器将揭示哺乳动物细胞膜的脂质和蛋白质成分如何相互作用，产生负责能量转导、跨膜运输和分子识别的功能组件。该仪器将表征脂-脂和脂-蛋白相互作用，这些相互作用控制着脂质双层组装的流动性和作为化学反应和分子运动驱动力的组件之间的热能流动。该仪器将在双色泵浦探测方案中使用可调谐皮秒激光，以检测双层膜和捕光蛋白质中的振动能量转移和快速分子尺度运动。这样的测量以前是不可能的。该检测系统是相敏的，并受散粒噪声限制，可以测量107个部分中的一个部分的传输变化。由于短寿命复合体在膜中形成和衰变的反应动力学是由振动激活的跨越障碍过程控制的，因此利用所提出的仪器获得的信息对于理解与空间非均相结构相关的动力学至关重要，包括脂筏和蛋白质。广泛使用的仪器的建立将对密歇根州立大学和区域科学界以及全球科学界产生重大影响，它将推动测量脂质双层性质和动力学的最先进水平。他们与密歇根州立大学的其他系(如生物化学和分子生物学、食品安全和毒理学、细胞和分子生物学、微生物学和分子遗传学)、附近机构(如萨吉诺山谷州立大学、西密歇根大学)和国际机构(如波兰华沙大学、英国巴斯大学、新加坡国立大学和陕西师范大学)的教师合作。他们还与联邦研究组织合作，如位于伊利诺伊州香槟的美国陆军工程师研究和开发中心。扩大科学领域中代表性不足群体的范围是至关重要的。密歇根州立大学制定了多个计划，以联系高中(密歇根州立大学高中荣誉科学/数学/工程计划(HSHSP)、ACS项目种子计划)、本科生(全国黑人化学家和化学工程师组织(NOBCChE)、德鲁/TAC计划)、研究生(NOBCChE、密歇根州立大学非裔美国人、拉丁裔(A)/奇卡诺(A)、亚洲/太平洋美国人和美洲原住民(ALANA)计划)和研究生水平(密歇根州立大学资助的少数族裔博士后奖学金)。PI和共同PI在几个层面上与这些项目合作，并继续努力为来自所有群体的学生提供实践研究机会和指导。

AbstractThis proposal is for the construction of an instrument that will provide previously unobtainable information on the organization and dynamics of plasma membranes, biomimetic structures, and light harvesting proteins. The dissipation of energy within lipid bilayers and light harvesting proteins is not well understood but is thought to mediate the function of these two different classes of biomolecular systems. One of the broad biological issues this project addresses is the fundamental, molecular basis for the formation of lipid raft structures, and why such structures vary with the concentrations and identities of the bilayer constituents. Understanding the molecular structural basis for lipid raft organization requires that the viscoelastic properties and intermolecular interactions of the lipid bilayer constituents can be measured. The proposed instrumentation will allow for the measurement of molecular motion and thermal energy flow in biomolecular systems. This project entails designing, constructing, and characterizing an instrument that will apply stimulated-emission spectroscopy to the study of structure and dynamics of biological membranes and proteins. The instrument will reveal how the lipid and protein components of the mammalian cell membrane interact to yield functional assemblies that are responsible for energy transduction, transmembrane transport, and molecular recognition. The instrument will characterize the lipid-lipid and lipid-protein interactions that control the fluidity of the lipid bilayer assembly and the flow of thermal energy between components that serves as the driving force for chemical reactions and molecular motion.The instrument will employ tunable picosecond lasers in a two-color pump?probe detection scheme to examine vibrational energy-transfer and fast molecular-scale motions in bilayer membranes and light harvesting proteins. Such measurements have not been possible before. The detection system is phase-sensitive and shot-noise-limited to measure transmission changes of one part in 107. Because the reaction dynamics underlying the formation and decay of short-lived complexes in membranes are controlled by vibrationally activated barrier-crossing processes, the information obtained with the proposed instrument is crucial to reaching an understanding of the dynamics associated with spatially heterogeneous structures, including lipid rafts and proteins. The creation of broadly accessible instrumentation that advances the state of the art in the measurement of lipid bilayer properties and dynamics will have a major impact on the MSU and regional scientific communities as well as on the global scientific community. The PI and co-PIs collaborate with faculty in a host of other MSU departments (e.g. Biochemistry and Molecular Biology, Food Safety and Toxicology, Cell and Molecular Biology, Microbiology and Molecular Genetics), faculty from nearby institutions (e.g. Saginaw Valley State University, Western Michigan University) and from international institutions (e.g. University of Warsaw (Poland), University of Bath (UK), National University of Singapore, and Shaanxi Normal University (PRC)). They also collaborate with Federal research organizations such as the US Army Engineer Research and Development Center in Champaign, IL. Broadening inclusion of under-represented groups in science is critically important. Michigan State University has multiple programs in place to connect with under-represented groups at the high school (MSU High School Honors Science/Math/Engineering Program (HSHSP), ACS Project SEED), undergraduate (National Organization of Black Chemists and Chemical Engineers (NOBCChE), DREW/TAC Program), graduate (NOBCChE, MSU African-American, Latino(a)/Chicano(a), Asian/Pacific American, and Native American (ALANA) Program) and post-graduate levels (MSU sponsored minority post-doctoral fellowships). The PI and the co-PIs have collaborated with these programs on several levels and continue to strive to provide students from all groups with hands-on research opportunities and mentoring.