CAREER: Engineering approaches to control collective cell migration using electrotaxis

职业：利用趋电性控制集体细胞迁移的工程方法

• 批准号: 2046977
• 负责人: Daniel Cohen
• 金额: $ 55.5万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2046977&HistoricalAwards=false
• 关键词: CAREER; Engineering; approaches; control; collective

The ability to direct the migration of cells in living tissues could accelerate wound healing or slow the spread of cells in diseases like cancer. Cell movement in the body has been shown to be influenced by local electrochemical fields. This behavior, called electrotaxis, can be directed by the external application of electric fields. Deepening our knowledge of electrotaxis will enable the development of tools to direct cell migration. This project also includes several education initiatives, including a yearly, week-long ‘Science Storytelling’ training workshop to help young scientists learn how to share the stories behind their research with the public. This project combines mechanistic understanding with engineering control. It merges primary skin tissue and new electro-bioreactor technology to establish a connection between native collective cell behaviors and our ability to control them. This should help to better apply electrotaxis as a tool for biotechnology. Aim 1 calls for a comprehensive characterization of how biophysical aspects of a tissue (shape, size, cell-cell adhesion) and electric field strength act as a ‘gas pedal’ affecting our ability to accelerate migration and increase forward tissue motion. Aim 2 defines how electrotaxis physically reprograms key migratory machinery needed for cell migration, with emphasis on determining necessary end-effectors and possible pharmacological ways to target them to improve electrotaxis. Aim 3 characterizes how native cell-cell interactions actually compete with electrotactic control and develops new approaches to mitigate this problem. Together, these aims will deliver fundamental ‘design rules’ for electrotaxis and use these rules to demonstrate how next-generation bioelectric interfaces will enable a fundamentally new way to engineer living tissue.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.

在活组织中引导细胞迁移的能力可以加速伤口愈合或减缓癌症等疾病中细胞的扩散。体内的细胞运动已被证明受到局部电化学场的影响。 这种行为称为趋电性，可以通过外部电场的应用来指导。加深我们对趋电性的了解将有助于开发指导细胞迁移的工具。该项目还包括几项教育举措，包括每年一次的为期一周的“讲科学故事”培训研讨会，以帮助年轻科学家学习如何与公众分享他们研究背后的故事。该项目将机械理解与工程控制相结合。它融合了原代皮肤组织和新的电生物反应器技术，在原生集体细胞行为和我们控制它们的能力之间建立了联系。这将有助于更好地应用趋电性作为生物技术的一种工具。目标1要求对组织的生物物理方面（形状、大小、细胞-细胞粘附）和电场强度如何作为影响我们加速迁移和增加向前组织运动的能力的“油门踏板”进行全面表征。目的2定义了趋电性如何物理地重新编程细胞迁移所需的关键迁移机制，重点是确定必要的末端效应子和可能的药理学方法来靶向它们以改善趋电性。目标3描述了原生细胞-细胞相互作用实际上是如何与趋电控制竞争的，并开发了新的方法来缓解这个问题。这些目标将共同为趋电性提供基本的“设计规则”，并使用这些规则来展示下一代生物电接口将如何实现一种全新的方式来工程化活组织。该奖项反映了NSF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。