Membrane fluidity: Both fundamental and functional

膜流动性：基础性和功能性

• 批准号: 2121854
• 负责人: Edward Lyman
• 金额: $ 73.86万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2121854&HistoricalAwards=false
• 关键词: Membrane; fluidity; Both; fundamental; functional

The membranes which enclose our cells are very thin sheets — not solid like a balloon, but rather fluid, like a soap film. Embedded in the membrane are a plethora of molecules that conduct the chemical conversation between the cell and the world outside. This chemical conversation (or “signaling”) underlies both normal functions, like exchange of neurotransmitters in the brain, and abnormal ones, like cancer growth and progression. But what choreographs signaling, so that partners find each other at the appropriate place and time? A crucial part of the answer is the viscosity of the membrane — Is it thick like honey, or thin like water? Measuring the viscosity of a cell membrane in an experiment is extremely challenging, and interpretation of the results relies on difficult to test assumptions. This project will therefore combine several different experimental measurements with detailed simulations of membranes. The simulations (which utilize federally funded supercomputers) are designed to fill in the gaps in the experiments, so that together they provide a complete understanding of the chemical origins of membrane viscosity. Through a collaboration with the Delaware Teachers Institute the research team will develop a series of lessons on the biophysics of fluids, which will be disseminated to twelve Delaware high school teachers. This content will both enrich the curricula of high schools throughout the state, and also expose students to the field of biophysics as a possible course of study for students who are strong in math, but also excited by developments in biology and health sciences.Cells actively regulate the fluidity of their membranes in response to changes in external conditions, like temperature, salinity, or pressure. Sinensky discovered this “homeoviscous adaptation” in the 1970’s, in bacteria that were grown at different temperatures, yet maintained constant fluidity. Despite the fundamental importance of membrane fluidity, it is still not understood how it emerges from the complex milieu of the cell membrane. Indeed, experimental measurements differ in their reports of membrane viscosity by more than a factor of ten, depending on the technique and how the measurement is interpreted. This knowledge gap will be filled by a combination of detailed simulations of membranes and several types of experiments. The simulations will use the most accurate and detailed models for membranes and will leverage federally funded supercomputing platforms. The experiments cover length and timescales from picoseconds to microseconds, and will use federally funded beamlines (neutron scattering at the National Institute of Standards and Technology and x-ray scattering Brookhaven National Lab). By integrating the simulations and experiments the investigators will resolve discrepancies in existing measurements and identify what factors determine membrane viscosity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

包围我们细胞的膜是非常薄的薄片--不像气球那样是固体，而是像肥皂膜那样的液体。嵌入细胞膜中的是大量的分子，它们在细胞与外界之间进行化学反应。这种化学转换（或“信号”）是正常功能（如大脑中神经递质的交换）和异常功能（如癌症的生长和发展）的基础。但是，什么样的舞蹈信号，使合作伙伴找到对方在适当的地点和时间？答案的一个关键部分是膜的粘度-它是像蜂蜜一样厚，还是像水一样薄？在实验中测量细胞膜的粘度是极具挑战性的，并且结果的解释依赖于难以测试的假设。因此，该项目将结合联合收割机几个不同的实验测量与详细的模拟膜。模拟（利用联邦资助的超级计算机）旨在填补实验中的空白，以便共同提供对膜粘度化学起源的完整理解。通过与特拉华州教师研究所的合作，研究小组将开发一系列关于流体生物物理学的课程，这些课程将分发给12名特拉华州高中教师。这一内容不仅丰富了全州高中的课程，也使学生接触到生物物理学领域，这是一门适合数学较强，但也对生物学和健康科学的发展感到兴奋的学生的课程。细胞会主动调节细胞膜的流动性，以响应外部条件的变化，如温度，盐度或压力。Sinensky在20世纪70年代发现了这种“稳态粘性适应”，在不同温度下生长的细菌中，仍然保持恒定的流动性。尽管膜流动性的基本重要性，它仍然不明白它是如何从细胞膜的复杂环境中出现的。事实上，实验测量结果在膜粘度的报告中相差超过10倍，这取决于技术和如何解释测量结果。这一知识缺口将通过详细的膜模拟和几种类型的实验相结合来填补。模拟将使用最准确和详细的膜模型，并将利用联邦资助的超级计算平台。这些实验涵盖了从皮秒到微秒的长度和时间尺度，并将使用联邦政府资助的光束线（美国国家标准与技术研究所的中子散射和布鲁克海文国家实验室的x射线散射）。通过整合模拟和实验，研究人员将解决现有测量中的差异，并确定哪些因素决定膜粘度。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。