CAREER: Engineering approaches to control collective cell migration using electrotaxis

引导活组织中细胞迁移的能力可能会加速伤口愈合，或减缓癌症等疾病中细胞的扩散。细胞在体内的运动已被证明受到局部电化学场的影响。这种行为被称为趋电性，可以由电场的外部施加来指导。加深我们对趋电性的了解将使指导细胞迁移的工具的开发成为可能。该项目还包括一些教育举措，包括每年一次、为期一周的“科学讲故事”培训讲习班，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。它融合了原生皮肤组织和新的电生物反应器技术，在天然集体细胞行为和我们控制它们的能力之间建立了联系。这应该有助于更好地将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、细胞与细胞的粘附性)和电场强度如何充当影响我们加速迁移和增加组织向前运动的能力的‘气踏板’进行全面的表征。目的2明确了趋电性如何在物理上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物和可能的药理学方法，以针对它们来改善趋电性。AIM 3描述了天然细胞-细胞相互作用实际上是如何与电极化控制竞争的，并开发了新的方法来缓解这一问题。总而言之，这些目标将为电动技术提供基本的‘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法来设计活组织。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。

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.