CAREER: Physical Regulation of Cell Migration by the Glycocalyx

这个教师早期职业发展计划（CAREER）项目将研究细胞如何在狭窄的空间中迁移。所有的细胞都被一层富含糖的长分子包裹着，称为糖萼。 糖萼在许多致命疾病中发生了巨大的变化，但人们对这种细胞涂层的变化如何使疾病变得更好或更糟知之甚少。 该项目将为糖萼的机械性能的精密工程创造新的工具。 它们将用于确定糖萼在细胞迁移中的作用。 细胞迁移对许多疾病的进展至关重要。 例如，该项目的结果可能导致防止转移性癌细胞扩散的新方法。 用于糖萼工程的工具预计将广泛应用于生物技术中，以在细胞上产生保护性和抗粘附涂层，用于各种应用，包括基于细胞的治疗和用于生物制造的细胞生产系统。因此，这项研究的结果将比基础研究更重要。 该项目还将包括一个全面的教育和推广计划，向初中和高中学生介绍物理生物学，目标是增加经济弱势群体和其他代表性不足的群体在科学，技术，工程和数学（STEM）学科中的参与。 最近的研究强调，细胞可以在3D环境中独立于整合素迁移，其中糖萼被认为提供对细胞外基质（ECM）的牵引力以用于推进。 尽管糖萼在细胞迁移和机械转导中的作用越来越受到重视，但我们对糖萼结构及其在细胞运动中的确切作用机制的整体物理理解仍然很原始。 这项研究将通过开发一种新的工具包来解决这一挑战，该工具包用于糖萼的精确工程和应用，沿着纳米级成像方法，以了解糖萼在细胞迁移中的物理功能。 该研究将测试特定的假设，即糖萼提供物理线索，指导在受限的3D环境中获得特定的迁移表型。 开发的工具和基础知识将广泛地与理解糖萼在正常生理学和疾病特异性环境中的功能相关。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

This Faculty Early Career Development Program (CAREER) project will investigate how cells migrate in narrow spaces. All cells are coated in a sugar-rich coating of long molecules called a glycocalyx. The glycocalyx changes dramatically in many lethal diseases, but little is known about how changes in this cell coating make a disease better or worse. This project will create new tools for precision engineering of the mechanical properties of the glycocalyx. They will be used to determine the role of glycocalyx in cell migration. Cell migration is crucial in how many diseases progress. For example, the results of the project could lead to new approaches to preventing the spread of metastatic cancer cells. The tools for glycocalyx engineering are expected to be applied broadly in biotechnology to generate protective and anti-adhesive coatings on cells for diverse applications, including cell-based therapies and cellular production systems for bio-manufacturing. Therefore, results from this research will be important beyond basic research. The project will also include a comprehensive education and outreach program that introduces middle and high school students to physical biology with the goal of increasing participation of economically disadvantaged and other under-represented groups in science, technology, engineering, and math (STEM) subjectsPhysical forces generated by and acting on cells directly influence tissue homeostasis and progression to disease states. Recent studies emphasize that cells can migrate independent of integrins in 3D environments, where the glycocalyx is believed to provide traction against the extracellular matrix (ECM) for propulsion. Despite the growing appreciation for the role of the glycocalyx in cell migration and mechanotransduction, our overall physical understanding of the structure and its precise mechanisms of action in cell motility remain primitive. The research will address this challenge through development of a new toolkit for precision engineering of the glycocalyx and application of the toolkit, along with nanoscale imaging approaches, to understand the physical function of the glycocalyx in cell migration. The research will test the specific hypothesis that the glycocalyx provides physical cues that direct acquisition of specific migration phenotypes in confined 3D environments. The tools and fundamental knowledge developed will be broadly relevant in understanding the function of the glycocalyx in normal physiology and disease-specific contexts.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.