CAREER: Symmetry and Geometry in Biological Active Matter

职业：生物活性物质的对称性和几何形状

• 批准号: 1848247
• 负责人: Nikta Fakhri
• 金额: $ 72.24万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1848247&HistoricalAwards=false
• 关键词: CAREER; Symmetry; Geometry; Biological; Active

The fundamental questions that the PI aims to address in this CAREER project are: What are the principles underlying the formation of spatio-temporal patterns of Rho GTPases, and what is their functional role in regulating the mechanics of the cell cortex and cell deformation? What is the feedback between cell shape changes and cytoplasmic flow induced by mechanical (dynamic) deformation of the cell cortex and the chemical pattern of Rho GTPases? To address these questions, the PI will combine experiment and theory to identify the fundamental principles underlying this interplay between chemical patterns and mechanical cell deformations and thereby to lay the foundation for a comprehensive understanding of the dynamics of mechano-chemical patterns in animal cells. Uncovering the principles of mechano-chemical structure formation in biological systems will also facilitate new smart materials and soft robotics technology. The proposed research activities will be closely integrated with teaching activities at the interface of physics and biology. (i) The PI will continue to mentor high school students through the Research Science Institute at MIT. (ii) As a faculty mentor for the MIT Summer Research Program (MSRP) General, the PI will continue to mentor and to attract underrepresented students (minorities, women in STEM, or students with low socioeconomic status) to MIT to gain significant research experience and explore the possibility of doctoral education at MIT.This project will combine novel experimental techniques, theory and mathematical modeling to elucidate how active mechanics and cell geometry, when coupled to chemical reactions, give rise to robust mechano-chemical patterns. Important life processes common to all animal cells such as cytokinesis and cellular migration require the interplay and coordination between chemical protein patterns and mechanical deformation of the cell shape. At the heart of both are active processes, driven and regulated by the highly conserved Rho family of GTPases and the action of myosin motors consuming ATP. Over the course of this project, the PI will construct, implement and experimentally validate a comprehensive theoretical model to quantify and to understand the mechanisms of mechano-chemical coupling between chemical patterns of Rho GTPases, mechanical cell deformations, and cytoplasmic flow. Starfish oocytes will be used as a biological model system to study mechano-chemical patterns during development in vivo, as they are a well-established system with a high degree of experimental accessibility. A novel imaging platform based on near-IR fluorescent single-walled carbon nanotubes will be developed to generate high resolution maps of cortex dynamics and mechanics during development. It will be combined with in vivo imaging of signaling protein localization, as well as biochemical, biophysical and optogenetic manipulations. As Rho GTPases are ubiquitous and in particular associated to the dynamic spatial structuring of cells, the investigations should reveal universal principles for the interplay of mechanical deformations and biochemical pattern formation.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Cellular Dynammics and Function Cluster in the Division of Molecular and Cellular Biosciences.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.

PI旨在解决这个CAREER项目的基本问题是：Rho GTP酶时空模式形成的基本原理是什么，它们在调节细胞皮质和细胞变形机制中的功能作用是什么？什么是细胞形状变化和细胞质流动之间的反馈诱导的机械（动态）变形的细胞皮质和Rho GTP酶的化学模式？为了解决这些问题，PI将联合收割机实验和理论相结合，以确定化学模式和机械细胞变形之间相互作用的基本原理，从而为全面了解动物细胞中机械化学模式的动力学奠定基础。揭示生物系统中机械化学结构形成的原理也将促进新的智能材料和软机器人技术。拟议的研究活动将与物理学和生物学接口的教学活动紧密结合。(i)PI将继续通过麻省理工学院的研究科学研究所指导高中生。(ii)作为麻省理工学院夏季研究计划（MSRP）的教师导师，PI将继续指导和吸引代表性不足的学生（少数族裔、STEM领域的女性或社会经济地位较低的学生）到麻省理工学院获得重要的研究经验，并探索在麻省理工学院接受博士教育的可能性。这个项目将联合收割机结合新颖的实验技术，理论和数学建模，以阐明如何主动力学和细胞几何形状，当耦合到化学反应，产生强大的机械化学模式。所有动物细胞共同的重要生命过程，如胞质分裂和细胞迁移，需要化学蛋白质模式和细胞形状的机械变形之间的相互作用和协调。两者的核心是活性过程，由高度保守的Rho GTP酶家族和消耗ATP的肌球蛋白马达的作用驱动和调节。在这个项目的过程中，PI将构建，实施和实验验证一个全面的理论模型，以量化和理解Rho GTP酶，机械细胞变形和细胞质流动的化学模式之间的机械化学耦合机制。海星卵母细胞将被用作生物模型系统，以研究体内发育过程中的机械化学模式，因为它们是一个成熟的系统，具有高度的实验可及性。将开发一种基于近红外荧光单壁碳纳米管的新型成像平台，以在开发过程中生成皮质动力学和力学的高分辨率地图。它将与信号蛋白定位的体内成像以及生物化学、生物物理学和光遗传学操作相结合。由于Rho GTP酶是普遍存在的，特别是与细胞的动态空间结构相关，研究应该揭示机械变形和生物化学模式形成相互作用的普遍原则。该项目由物理学系的生命系统物理学计划和分子与细胞生物科学系的细胞动力学和功能群共同支持。该奖项反映了NSF的法定使命，并已被认为是值得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的支持。

项目成果

Topological braiding and virtual particles on the cell membrane

• DOI: 10.1073/pnas.2104191118
• 发表时间: 2021-08-24
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Liu, Jinghui;Totz, Jan F.;Fakhri, Nikta
• 通讯作者: Fakhri, Nikta

Dissipative timescales from coarse-graining irreversibility

粗粒度不可逆性的耗散时间尺度

• DOI: 10.1088/1742-5468/acdce6
• 发表时间: 2023
• 期刊: Journal of Statistical Mechanics: Theory and Experiment
• 作者: Cisneros, Freddy A;Fakhri, Nikta;Horowitz, Jordan M
• 通讯作者: Horowitz, Jordan M

A hierarchy of protein patterns robustly decodes cell shape information

蛋白质模式的层次结构可以稳健地解码细胞形状信息

• DOI: 10.1038/s41567-021-01164-9
• 发表时间: 2021
• 期刊: Nature Physics
• 影响因子: 19.6
• 作者: Wigbers;Brauns;Swartz;Fakhri
• 通讯作者: Fakhri

Symmetry, Thermodynamics, and Topology in Active Matter

• DOI: 10.1103/physrevx.12.010501
• 发表时间: 2022-02-11
• 期刊: PHYSICAL REVIEW X
• 影响因子: 12.5
• 作者: Bowick, Mark J.;Fakhri, Nikta;Ramaswamy, Sriram
• 通讯作者: Ramaswamy, Sriram

Topological turbulence in the membrane of a living cell

• DOI: 10.1038/s41567-020-0841-9
• 发表时间: 2020-06
• 期刊: Nature Physics
• 影响因子: 19.6
• 作者: Tzer Han Tan;Jinghui Liu;Pearson W. Miller;Melis Tekant;J. Dunkel;N. Fakhri