The Biophysics of Collective Cell Locomotion

集体细胞运动的生物物理学

• 批准号: 2209494
• 负责人: Calina Copos
• 金额: $ 30.09万
• 依托单位: Northeastern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2209494&HistoricalAwards=false
• 关键词: Biophysics; Collective; Cell; Locomotion

For a single fertilized egg cell to form into an embryo, there are many intermediate steps, including repeated cell division and development of organs in the correct location. But the details of this process and its regulation have yet to emerge. For example, in the sea squirt -- a simpler system than the human embryo but one that shares a lot of commonalities -- a pair of cells is the starting point of the heart of this organism. These cells must move from their origin to the future location of the heart guided by cues from inside the embryo. As the paired cells move, they must push other cells out of their path to reach their destination, all while not losing contact with each other. Although observational studies of the coordinated movement of groups of cells involved in organ formation advance knowledge of embryonic development and associated congenital conditions, this project will deepen understanding by employing mathematical modeling and computer simulations to tease out the many facets of this process. The project will involve developing new computer simulation schemes for the mechanical interactions between cell boundary and interior dynamics, new models for the biochemistry needed to initiate collective migration, new methods for efficiently solving equations in deforming, moving geometries, and extensions to full three-dimensional domains. The investigators will use the interdisciplinary nature of the project to recruit and train undergraduate and graduate students. The study of collective locomotion of organisms has led to important mathematical models that have guided biological discovery. A distinguishing feature of this project is that the multi-body interaction is achieved through mechanochemical bonds that interact with the cell's biochemistry and biomechanics in an unknown way. We focus on the collective migration of two cells in the early stages of heart development of the sea squirt Ciona intestinalis, an important model organism. Initially, these two cells are indistinguishable, yet at some point they establish leader and follower roles and move with distinct morphologies, squeezing through deformable tissues. Experiments show there is an advantage to move as a cohesive pair rather than a single cell, however, it is unclear why two cells do not slow each other down. These observations lead to the following questions: How are intracellular mechanics integrated to give rise to motility as a cohesive group? Why can two cells move faster together than alone? Is the two-cell system better at polarization and initiating migration than an individual cell? Mathematical modeling can aid experiments in answering these questions, but numerical solutions of the model equations will require development of novel computational methods that will be able to simulate coupled mechanical, transport, and chemical reaction equations in complex evolving geometries. Collaboration with an experimental lab will result in the discovery of a set of minimal yet sufficient interactions underlying the mechanical and biochemical organization of a cohesive cell group.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.

一个受精卵细胞要形成一个胚胎，需要经过许多中间步骤，包括细胞的重复分裂和器官在正确位置的发育。但这一过程及其监管的细节尚未浮出水面。例如，在海鞘中——一个比人类胚胎更简单的系统，但有很多共同点——一对细胞是这个有机体心脏的起点。这些细胞必须在胚胎内部信号的引导下，从它们的起源地移动到心脏的未来位置。当成对的细胞移动时，它们必须将其他细胞挤出到达目的地的路径，同时保持彼此之间的联系。虽然对参与器官形成的细胞群协调运动的观察研究促进了对胚胎发育和相关先天性疾病的认识，但该项目将通过使用数学建模和计算机模拟来梳理这一过程的许多方面，从而加深对这一过程的理解。该项目将涉及开发新的计算机模拟方案，用于细胞边界和内部动力学之间的机械相互作用，启动集体迁移所需的生物化学新模型，有效解决变形，移动几何形状方程的新方法，以及扩展到全三维域。研究人员将利用该项目的跨学科性质来招募和培训本科生和研究生。对生物体集体运动的研究产生了重要的数学模型，这些模型指导了生物学的发现。这个项目的一个显著特点是，多体相互作用是通过机械化学键来实现的，这种键以一种未知的方式与细胞的生物化学和生物力学相互作用。我们重点研究了海鞘（一种重要的模式生物）心脏发育早期两个细胞的集体迁移。最初，这两种细胞难以区分，但在某种程度上，它们建立了领导者和追随者的角色，并以不同的形态移动，挤压可变形的组织。实验表明，作为一对有凝聚力的细胞移动比单个细胞移动有优势，然而，尚不清楚为什么两个细胞不会互相减慢速度。这些观察结果导致了以下问题：细胞内力学是如何结合起来产生运动作为一个有凝聚力的群体的？为什么两个细胞合在一起比单独移动快？双细胞系统在极化和启动迁移方面是否优于单个细胞？数学建模可以帮助实验回答这些问题，但模型方程的数值解将需要开发新的计算方法，以便能够模拟复杂演化几何中的耦合力学、输运和化学反应方程。与实验实验室的合作将导致发现一组最小但充分的相互作用，这些相互作用是内聚细胞群的机械和生化组织的基础。该奖项反映了美国国家科学基金会的法定使命，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。

项目成果

Author Correction: Stress fibres are embedded in a contractile cortical network

作者更正：应力纤维嵌入收缩皮质网络中

• DOI: 10.1038/s41563-020-00862-8
• 发表时间: 2021
• 期刊: Nature Materials
• 影响因子: 41.2
• 作者: Vignaud, Timothée;Copos, Calina;Leterrier, Christophe;Toro-Nahuelpan, Mauricio;Tseng, Qingzong;Mahamid, Julia;Blanchoin, Laurent;Mogilner, Alex;Théry, Manuel;Kurzawa, Laetitia
• 通讯作者: Kurzawa, Laetitia

Supracellular organization confers directionality and mechanical potency to migrating pairs of cardiopharyngeal progenitor cells.

• DOI: 10.7554/elife.70977
• 发表时间: 2021-11-29
• 期刊: eLife
• 影响因子: 7.7
• 作者: Bernadskaya YY;Yue H;Copos C;Christiaen L;Mogilner A
• 通讯作者: Mogilner A

Electric field-guided collective motility initiation of large epidermal cell groups.

• DOI: 10.1091/mbc.e22-09-0391
• 发表时间: 2023-05-01
• 期刊: MOLECULAR BIOLOGY OF THE CELL
• 影响因子: 3.3
• 作者: Sun, Yaohui;Reid, Brian;Zhang, Yan;Zhu, Kan;Ferreira, Fernando;Estrada, Alejandro;Sun, Yuxin;Draper, Bruce W.;Yue, Haicen;Copos, Calina;Lin, Francis;Bernadskaya, Yelena Y.;Zhao, Min;Mogilner, Alex
• 通讯作者: Mogilner, Alex

Actin Turnover Required for Adhesion-Independent Bleb Migration

不依赖粘附的泡迁移所需的肌动蛋白周转率

• DOI: 10.3390/fluids7050173
• 发表时间: 2022
• 期刊: Fluids
• 影响因子: 1.9
• 作者: Copos, Calina;Strychalski, Wanda
• 通讯作者: Strychalski, Wanda