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CAREER: Understanding the interplay between lipid composition and biomolecule transport in biological membranes

职业：了解生物膜中脂质成分与生物分子运输之间的相互作用

基本信息

批准号：
1942581
负责人：
Peter Beltramo
金额：
$ 59.23万
依托单位：
University of Massachusetts Amherst
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942581&HistoricalAwards=false
关键词：
CAREER Understanding interplay between lipid

项目摘要

The phospholipid membrane is the barrier that divides the interior and exterior of cells. It is laden with membrane-bound objects such as proteins and ion channels which are under constant motion and dictate various functions of the cell. Unraveling the role of the phospholipid membrane and the significance of high concentrations of membrane proteins in biological signaling processes could lead to an improved understanding of how cells communicate, transport material, and orchestrate essential processes. These discoveries can, in turn, enable new advanced drug delivery systems, biosensors, and other biomimetic materials. This CAREER award will support the development of experimental methods to create robust artificial mimics of cell membranes, quantify their properties, and determine the interplay between those properties and the dynamics and transport properties of membrane-bound objects. The project will help advance one of NSF’s Big Ideas- Understanding the Rules of Life - by addressing a fundamental question in biology: how is material and information transported between cells? This research will be integrated with a robust educational component that includes workshops training K-12 educators on how to translate challenging concepts in engineering, biology, and chemistry into interactive classroom demos, the recruitment of underrepresented undergraduate students from local community colleges in the Pioneer Valley for summer research internships, and the development of a new course to strengthen student understanding relationships between chemical engineering research, industry, and the economy.The cell membrane plays an outsized role in many biological processes due to the presence of large concentrations of peripheral and integral membrane proteins that selectively regulate the transport of material and information across the barrier. Selective transport across the membrane has been exploited to develop biosensors, but most work relies on monitoring the transport across a single ion channel. Developing technologies that leverage the heterogeneity and high concentrations of ion channels could enable multiplexed biosensing with improved signal-to-noise and throughput. However, changing elastic properties of protein-laden membranes, membrane deformations, and crowding effects can alter transport characteristics. Therefore, this project aims to understand how the properties of the phospholipid bilayer in biologically relevant membranes alter the spatiotemporal dynamics of membrane bound objects. A novel experimental platform to fabricate planar, freestanding, artificial cell membranes and measure membrane properties (thickness, lateral elasticity, Young’s modulus) will be extended to incorporate leaflet asymmetry. Controlled quantities of membrane bound microparticles will be introduced and microrheological techniques will be applied to reveal fundamental insight into thin film rheology and the two-dimensional hydrodynamics of crowded membranes. By utilizing simultaneous optical monitoring of the membrane by fluorescence microscopy and electrophysiological techniques to measure ion transport, the concentration-dependent diffusion and gating activity of ion channels will also be investigated. The objectives of this CAREER award are to provide insight into how biological membranes regulate intracellular transport by 1) evaluating the change in elastic properties in membranes mimicking different types of cells, 2) determining the modification of lateral dynamics as membranes become increasingly covered with peripheral objects, and 3) quantifying the concurrent alteration in trans-bilayer ion transport.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.

磷脂膜是分隔细胞内部和外部的屏障。它充满了膜结合的物体，如蛋白质和离子通道，它们处于不断的运动中，并决定了细胞的各种功能。解开磷脂膜的作用和高浓度膜蛋白在生物信号传导过程中的重要性，可以提高对细胞如何交流，运输物质和协调基本过程的理解。这些发现可以反过来使新的先进药物输送系统，生物传感器和其他仿生材料成为可能。该CAREER奖将支持实验方法的开发，以创建强大的人工模拟细胞膜，量化其特性，并确定这些特性与膜结合物体的动力学和运输特性之间的相互作用。该项目将通过解决生物学中的一个基本问题来帮助推进NSF的大想法之一-了解生命的规则：细胞之间的物质和信息是如何传输的？这项研究将与一个强大的教育组成部分，其中包括培训K-12教育工作者如何将工程，生物和化学中具有挑战性的概念转化为互动课堂演示的研讨会相结合，从先锋谷当地社区学院招募代表性不足的本科生进行夏季研究实习，以及一门新课程的开发，以加强学生对化学工程研究，工业，细胞膜在许多生物过程中起着巨大的作用，这是由于存在大浓度的外周和整合膜蛋白，其选择性地调节物质的运输，信息跨越屏障。选择性跨膜转运已被用于开发生物传感器，但大多数工作依赖于监测跨单个离子通道的转运。开发利用离子通道的异质性和高浓度的技术可以实现具有改善的信噪比和通量的多路生物传感。然而，改变载有蛋白质的膜的弹性性质、膜变形和拥挤效应可以改变运输特性。因此，这个项目的目的是了解生物相关膜中磷脂双层的性质如何改变膜结合物体的时空动力学。一种新型的实验平台，制造平面，独立，人工细胞膜和测量膜的性能（厚度，横向弹性，杨氏模量）将扩展到包括瓣叶不对称。控制量的膜结合微粒将被引入和microrhoreologic技术将被应用到揭示基本的洞察薄膜流变学和拥挤的膜的二维流体动力学。通过利用荧光显微镜和电生理学技术测量离子转运的膜的同时光学监测，还将研究离子通道的浓度依赖性扩散和门控活性。该CAREER奖的目的是通过以下方式深入了解生物膜如何调节细胞内转运：1）评估模拟不同类型细胞的膜中弹性特性的变化，2）确定随着膜越来越多地被周边物体覆盖，和3）定量反式-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知识产权评估的支持。优点和更广泛的影响审查标准。