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

磷脂膜是分隔细胞内部和外部的屏障。它装载着膜结合的物体，如蛋白质和离子通道，它们处于不断的运动中，并决定着细胞的各种功能。解开磷脂膜的作用和高浓度膜蛋白在生物信号传递过程中的重要性，可以更好地理解细胞如何沟通、运输物质和协调必要的过程。这些发现反过来可以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。该职业奖将支持开发实验方法，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对象的动力学和传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：物质和信息是如何在细胞之间传输的，来帮助推进NSF的一个重要想法--理解生命规则？这项研究将与强大的教育组成部分相结合，包括培训K-12教育工作者如何将具有挑战性的工程、生物和化学概念转化为互动课堂演示的讲习班，从先锋谷当地社区大学招募未被充分代表的本科生参加暑期研究实习，以及开发一门新课程以加强学生对化学工程研究、工业和经济之间的关系的理解。由于存在大量的外周和整体膜蛋白，选择性地调节物质和信息的跨障碍传输，细胞膜在许多生物过程中发挥着超大的作用。已经利用膜的选择性传输来开发生物传感器，但大多数工作依赖于监测单个离子通道的传输。开发利用离子通道的异质性和高浓度的技术可以实现多路生物传感，提高信噪比和吞吐量。然而，改变富含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，本项目旨在了解生物相关膜中磷脂双层的性质如何改变膜结合对象的时空动力学。一个新的实验平台将扩展到包括小叶不对称在内，该平台可以制造平面的、独立的人造细胞膜，并测量膜的属性(厚度、侧向弹性、杨氏模数)。将引入受控数量的膜结合微粒，并将应用微观流变学技术来揭示薄膜流变学和拥挤膜的二维流体动力学的基本见解。通过利用荧光显微镜和电生理技术同时对膜进行光学监测来测量离子传输，还将研究离子通道随浓度变化的扩散和门控活性。这项职业奖的目的是通过1)评估模拟不同类型细胞的膜中弹性性质的变化，2)确定随着膜变得越来越被外围物体覆盖而改变侧向动力学，以及3)量化跨双层离子运输的同时变化，来洞察生物膜如何调节细胞内的运输。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.