Toward Synthetic Neutrophils: De Novo Engineering of Chemotactic Artificial Cells

细胞迁移对许多生理过程和疾病状态都很重要，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。尽管细胞迁移在生物学上具有重要意义，但人们对允许细胞移动所需的最低要求知之甚少。该项目的目标是使用人工类细胞系统来确定细胞迁移的最低要求，并最终能够控制细胞在医学和生物技术中的应用。该项目将为高中生、研究生和研究生提供研究机会。趋化性在从胚胎发育到免疫反应的整个生物学过程中都扮演着重要的角色。尽管它的生理意义和过去几十年来的密集研究，仍然缺乏对细胞迁移行为背后的分子机制的充分了解。主要的挑战在于两种信号传递方式的复杂程度：涉及信号转导的生化反应和引起膜变形的生物力学作用。通过采取自下而上的方法，研究人员最近创造了一种由巨大的单层囊泡组成的人造细胞，在外部化学刺激的作用下，这种细胞可以经历对称性破坏。这种行为是细胞极化的特征，这是在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，该团队的目标是识别和组装囊泡内的最小一组生物分子，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，他们将创造独特的机会，促进本科生和研究生，特别是少数族裔和女性学生的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的课程--合成与计算细胞生物学。这门课程将连接不同的社区，并提高他们对这一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。这一奖项反映了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。

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.