Causes and Effects of Friction in Collective Cell Migration

这个项目将研究生物细胞如何在集体群体中移动。这是癌症侵袭、组织发育和伤口愈合过程中必不可少的过程。众所周知，这种运动是由细胞产生的力产生的。然而，这些力量如何平衡以创造运动尚不清楚。这种知识上的差距阻碍了控制迁移的努力，例如在癌症侵袭或伤口愈合方面。目前人们认为，摩擦力可以平衡每个电池产生的力。然而，没有一种既定的方法来测量摩擦力。这使得细胞产生的力量和集体运动之间的精确关系变得未知。该项目将测量摩擦力，并确定哪些生物物理因素增加或减少摩擦力。这项研究还将研究摩擦力如何影响细胞产生的力在一起迁移的一组细胞之间传递的距离。这些发现将为预测细胞力量如何导致集体迁移提供一种新的方法。这将是控制应用程序迁移以改善人类健康的第一步。这项工作将支持研究生和本科生的跨学科培训。它还将与教师研究体验计划合作，该计划将使高中教师能够在课堂上开展实践活动，将这项研究的主题应用到课堂上，这将使无数高中生有机会了解物理学和生物学的新应用。这项研究将通过设计测量摩擦的实验方法和确定控制摩擦的生物物理因素来推动该领域的发展。为此，将通过良好控制的实验和对细胞牵引力、应力和速度的严格测量相结合，量化细胞-衬底和细胞-细胞界面上的摩擦。细胞-底物和细胞-细胞界面摩擦的根本原因将通过扰动底物硬度、细胞-底物粘连、细胞-细胞粘连和肌动球蛋白收缩来系统地研究。此外，理论模型预测，电池-电池和电池-衬底界面的摩擦比设定了控制集体移动的电池组的大小的长度尺度。这项研究将量化这种长度尺度，以应对各种扰动，从而深入了解一种基于物理的机制，即每个细胞通过改变摩擦力，可以在比自身更大的长度尺度上影响集体运动--集体群体的尺度。识别这种连接长度尺度的机制对于理解复杂的多体系统(如集体细胞迁移)至关重要。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。

This project will study how biological cells move in collective groups. This is an essential process in cancer invasion, tissue development, and wound healing. It is known that the motion results from cell-generated forces. However, how the forces balance to create motion is not clear. This gap in knowledge hinders efforts to control the migration, for example in cancer invasion or wound healing. It is currently believed that a friction force balances the forces produced by each cell. However, there is no established way to measure the friction force. This makes the precise relationship between cell-generated forces and collective motion unknown. This project will measure friction and determine what biophysical factors increase or decrease friction. This research will also study how friction affects the distance over which cell-generated forces are transmitted across a group of cells migrating together. These findings will offer a new way to predict how cell forces bring about the collective migration. This will be the first step to controlling the migration for applications in improving human health. This work will support interdisciplinary training of both graduate and undergraduate students. It will also partner with a Research Experience for Teachers program that will enable a high school teacher to develop hands-on activities that apply topics of this research in the classroom, which will give countless high school students an opportunity to learn about new applications of physics and biology.This research will advance the field by designing experimental methods to measure friction and identifying the biophysical factors controlling friction. To this end, friction will be quantified both at the cell-substrate and cell-cell interfaces through a combination of well-controlled experiments and rigorous measurement of cell tractions, stresses, and velocities. The underlying causes of friction at the cell-substrate and cell-cell interfaces will be systematically studied by perturbing substrate stiffness, cell-substrate adhesions, cell-cell adhesions, and actomyosin contractility. Additionally, theoretical modeling predicts that the ratio of friction at the cell-cell and cell-substrate interfaces sets a length scale controlling the size of a collectively moving group of cells. The research will quantify this length scale in response to various perturbations, hence giving insight into a physics-based mechanism whereby each cell, by altering friction, can affect the collective motion on a length scale larger than itself--the scale of the collective group. Identifying mechanisms such as this one that bridge length scales is essential for understanding complicated, multi-body systems such as collective cell migration.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.