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

非技术摘要当你读到这句话时，数十亿件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之间运输。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。物理学家目前对微小(微米大小)粒子传输过程的理解不足以解释细胞被放在显微镜下时实际观察到的东西。该项目将在显微镜载玻片上创建细胞的“玩具模型”，并测量微小颗粒的传输以及与驱动传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，研究小组将经验性地确定改进细胞内运输过程的科学模型和理论所需的关键参数。此外，为了帮助培养、激励和多样化下一代科学家，每年夏天，首席研究员将自愿参加现有的大学前推广计划，为来自洛杉矶大都市区的六名成绩优异但贫困的十年级学生提供研究机会。然后，他们将由斯克里普斯学院的教职员工和在校本科生通过他们的大学申请和其他课程进行指导。技术摘要本项目的主要目标是促进我们对远离平衡的活性仿生材料中运输和机械性能之间关系的理解。真核细胞依赖于在动态、复杂和拥挤的环境中跨几十微米的分子从1 nm到1μm的靶向运输来维持生命。特别是，分子通过紧急传输机制聚集、混合和分离，其中非平衡动力学和分子拥挤引起的空间效应都起着至关重要的作用。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，并使用定制开发的具有光学捕获能力的光片显微镜同时表征被动和主动运输、网络连接、力响应和粘弹性系数。该项目旨在将实验结果和附带的理论模型相结合，以生成可在活体中验证的预测。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。

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.