Probing the Wave-Like Nature of Cell Migration and Collective Behavior

在这个项目中，pi将调查最近观察到的结果，即细胞支架的动力学在许多生物过程中都是波浪形的-从变形虫趋化性到发育。PI的目标是阐明运动机制的这种波状特征如何影响复杂环境中细胞的导航，以及细胞群的集体行为。pi将使用盘状棘球蚴作为一种模式生物，它既表现出个体细胞迁移行为，也表现出集体细胞迁移行为，即使细胞在没有任何表面接触的情况下悬浮，也表现出波状突起活动。具体目标是：1。波面耦合：pi将分析波如何与表面相互作用，使用微制造的局部粘附片和线来产生力和运动。目的是了解粘附模式如何指导迁移，并将这种见解整合到集体细胞迁移的随机模拟中。2. 细胞-细胞耦合：pi将测量波如何在接触的细胞群中传播，并将这一发现整合到模拟中。目的是阐明细胞-细胞信号传导和群体迁移的机械方面。3. 触发波和共振：pi将利用他们团队在非线性动力学、微加工和变形虫细胞迁移的定量研究方面的优势来实现这些目标。pi将通过结合控制3D微加工和局部粘附块的表面功能化，系统形状动力学量化和集体动力学随机建模的专业知识来开展拟议的工作。为了使他们的发现更广泛地传播，pi还将为YouTube开发一系列视频，突出波状细胞迁移和细胞-细胞通信，作为一个跳跃性的点，在一个适合公众的水平上介绍不同的科学主题。PI将在这个研究项目中培训妇女和未被充分代表的少数民族。所有学生都将接受涉及生物物理学和材料科学要素的高度跨学科培训。

In this project, the PIs will investigate the consequences of recent observations that the dynamics of the cell scaffolding is wavelike in many biological processes - from amoeboid chemotaxis to development. The PI's goal is to elucidate how this wave-like characteristic of the motility machinery affects navigation of cells in complex environments, and collective behavior of cell groups. The PIs will use D. discoideum as a model organism that exhibits both individual and collective cell migration behavior, and that exhibits wave-like protrusive activity even when cells are suspended without any surface contact. The specific goals are: 1. Wave-surface coupling: The PIs will analyze how waves interact with surfaces to generate forces and motion using micro-fabricated local adhesion patches and lines. The aim is to understand how patterns of adhesivity may direct migration and to integrate this insight into stochastic simulations of collective cell migration. 2. Cell-cell coupling: The PIs will measure how waves propagate through groups of cells that are in contact and integrate this finding in simulations. The aim is to elucidate mechanical aspects of cell-cell signaling and group migration. 3. Triggering waves and resonances: the PIs will use the strengths of their team in nonlinear dynamics, microfabrication, and quantitative studies of amoeboid cell migration, to achieve these goals. The PIs will carry out the proposed work through the combination of expertise in controlled 3D microfabrication and surface functionalization of local adhesion patches, systematic shape dynamics quantification, and stochastic modeling of collective dynamics. To make their findings broadly accessible, the PIs will also develop a series of videos for YouTube that will highlight wavelike cell migration and cell-cell communication as a jumping point to introduce different scientific topics at a level that is suitable for the general public. The PI will train women and underrepresented minorities in this research program. All students will receive highly interdisciplinary training involving elements of biophysics and materials science.