Toward Synthetic Neutrophils: De Novo Engineering of Chemotactic Artificial Cells

细胞迁移在许多生理过程和疾病条件中都很重要，包括血管生成、胚胎发育、伤口愈合、免疫防御、癌症转移、病原体感染和神经回路的建立。尽管细胞迁移具有重要的生物学意义，但对于允许细胞移动的最低要求知之甚少。该项目的目标是使用一种人造细胞样系统来定义细胞迁移的最低要求，并最终能够控制细胞的运动，用于医学和生物技术。该项目将为高中生、学士后学生和研究生提供研究机会。趋化性在从胚胎发育到免疫应答的整个生物学过程中发挥着重要作用。尽管在过去的几十年里，细胞迁移的生理意义和研究一直很激烈，但对细胞迁移行为的分子机制仍然缺乏充分的了解。主要的挑战源于两种信号传导模式的深刻复杂性：涉及信号转导的生化反应和诱导膜变形的生物力学驱动。通过自下而上的方法，研究人员最近制造了一种由巨大的单层囊泡组成的人造细胞，这种细胞在添加外部化学刺激时可能会发生对称性破坏。这种行为是细胞极化的特征，是天然趋化过程中观察到的关键事件之一。在这个实验系统的基础上，在理论建模的指导下，该团队的目标是在囊泡内识别和组装一组最小的生物分子，以产生所需类型的膜变形和运动性。基于其研究主题的跨学科性质，他们将为本科生和研究生，特别是少数民族和女性学生，创造独特的机会，促进STEM研究和教育。同时，他们将把现有的合成生物学课程扩展为一门新课程，“合成与计算细胞生物学”。本课程将连接不同的团体，并提高他们对这门跨学科学科在剖析复杂生物学基本原理方面的力量的认识。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。

Cell migration is important for many physiological processes and disease conditions, including angiogenesis, embryonic development, wound healing, immune defense, cancer metastasis, pathogen infection, and the establishment of neural circuits. Despite the biological importance of cell migration, relatively little is known about what is minimally required to allow a cell to move. The goals of this project are to use an artificial cell-like system to define the minimal requirements for cell migration and ultimately to be able to control the movements of cells for applications in medicine and biotechnology. This project will provide research opportunities for high school students, post-baccalaureate students and graduate students. Chemotaxis plays a fundamental role throughout biology ranging from embryonic development to immune response. Despite its physiological significance and intense research over last decades, there is still a lack of full understanding of the molecular mechanisms underlying cell migratory behaviors. The primary challenge is rooted in the profound complexity of two signaling modalities: the biochemical reactions that involve signal transduction and the biomechanical actuations that induce membrane deformations. By taking a bottom-up approach, the investigators recently generated an artificial cell made of giant unilamellar vesicles, which could undergo symmetry breaking upon addition of an external chemical stimulus. This behavior is characteristic of cell polarization, one of the key events observed during native chemotaxis. Built on this experimental system and guided by theoretical modeling, the team aims to identify and assemble a minimal set of biomolecules inside the vesicles to generate desired types of membrane deformations as well as motility. Based on the interdisciplinary nature of their research theme, they will create unique opportunities to promote STEM research and education for undergraduate and graduate students, particularly minority and female students. In parallel, they will expand an existing course on synthetic biology into a new course, “Synthetic and Computational Cell Biology”. This course will connect diverse communities and raise their awareness of the power of this interdisciplinary subject in dissecting basic principles of complex biology.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.