RUI: Anomalous and motor-driven dynamics in crowded biomimetic networks

当你读这句话的时候，数十亿的细胞货物正在通过许多紧密协调的物理机制在你体内的细胞中运输。我们细胞的内部是一个拥挤的三维网格，可以根据需要动态重组。物理学家目前对小（微米级）粒子的运输过程的理解不足以解释当细胞被置于显微镜下时实际观察到的情况。该项目将在显微镜载玻片上创建细胞的“玩具模型”，并测量小颗粒的运输以及与驱动运输的不同物理机制相对应的样品的机械响应。通过这种方式，研究团队将根据经验确定改善细胞内转运过程的科学模型和理论所需的关键参数。此外，为了帮助培训，激励和多样化的下一代科学家，每年夏天，首席研究员将志愿与现有的大学预科外展计划，提供研究机会，以六个高成就，但贫困的十年级学生从洛杉矶大都市区。然后，他们将通过他们的大学申请和超越斯克里普斯学院的教师和当前的本科生的指导。技术摘要这个项目的首要目标是推进我们的运输和远离平衡的活性，仿生材料的机械性能之间的关系的理解。真核细胞依赖于在动态、复杂和拥挤的环境中将分子从1 nm到1 μm靶向运输到数十微米，以维持生命。特别是，分子被包围，混合，并通过紧急运输机制分离，其中非平衡动力学和分子拥挤产生的空间效应都起着至关重要的作用。该研究小组将在显微镜载玻片上创建完全可调的拥挤和非平衡仿生环境，并使用定制开发的光捕获功能光片显微镜同时表征被动和主动传输，网络连接，力响应和粘弹性模量。该项目旨在将联合收割机的实验结果和相应的理论模型结合起来，以产生可在体内测试的预测。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Non-Technical Abstract As you read this sentence, billions of pieces of cellular cargo are being transported across the cells in your body via many tightly coordinated physical mechanisms. The inside of our cells is a crowded three-dimensional mesh which can restructure dynamically as needed. Physicists' current understanding of transport processes of small (micron-sized) particles is insufficient to explain what is actually observed when cells are placed under a microscope. This project will create "toy models" of cells on microscope slides and measure both the transport of small particles as well as the mechanical response of the sample corresponding to the different kinds of physical mechanisms driving the transport. In this way, the research team will empirically determine critical parameters needed to improve scientific models and theories on intracellular transport processes. Additionally, to help train, inspire, and diversify the next generation of scientists, each summer the principal investigator will volunteer with an existing pre-college outreach program to provide research opportunities to six high-achieving but underprivileged tenth-graders from the Los Angeles metropolitan area. They will then be mentored by faculty and current undergraduate students at Scripps College through their college applications and beyond.Technical Abstract The overarching goal of this project is to advance our understanding of the relationship between transport and mechanical properties within an active, biomimetic material far from equilibrium. Eukaryotic cells rely on targeted transport of molecules from 1 nm to as large as 1 μm across tens of microns in a dynamic, complex, and crowded environment to sustain life. In particular, molecules are corralled, mixed, and separated by emergent transport mechanisms where non-equilibrium dynamics and steric effects arising from molecular crowding both play crucial roles. The research team will create fully-tunable crowded and non-equilibrium biomimetic environments on microscope slides and simultaneously characterize the passive and active transport, network connectivity, force response, and viscoelastic moduli using a custom-developed optical trapping capable lightsheet microscope. This project aims to combine experimental results and accompanying theoretical models to generate predictions testable in vivo.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.