IRES Track I: Advanced Imaging and Characterization at the Interface Between Living and Nonliving Materials

该项目的目标是开发先进的成像技术和创新的显微探针，以确定生物细胞如何对力作出反应，并培训美国学生掌握这些技术。这些实验将帮助我们了解干细胞如何分化为功能性细胞类型，癌细胞如何扩散，以及血流如何被调节。了解细胞如何与环境相互作用对于开发各种健康相关问题的治疗方法至关重要，包括关节修复，癌症治疗，组织工程以及心脏和血管疾病的预防和治疗。科学目标将通过集中的国际合作来实现，为研究生和本科生提供密集的研究培训。每年，将有4 - 6名美国学生在利哈伊大学教授和法国波尔多大学国家实验室的研究人员的共同指导下进行博士或本科毕业论文的研究。每个参与的学生都将在夏季在波尔多的实验室工作，并在今年剩下的时间里在利哈伊工作。将考虑性别平衡和种族和民族多样性，以确保美国STEM劳动力在多元化、包容性和国际环境中发展。理哈伊大学科学与工程系的一个团队将与法国波尔多大学CNRS的研究人员合作，开展主题研究项目，旨在开发多尺度微流变学，以研究多细胞类器官的机械转导，3d打印支架中干细胞分化的延时共聚焦成像，以及磁性纳米颗粒介导的膜结合蛋白在支撑膜上的转运。该研究将开发三种模型系统：由亚毫米水凝胶胶囊限制的细胞器，3D打印的生物支架和嵌入磁性纳米颗粒标记的膜结合蛋白的支持脂质膜。多尺度成像方式，包括荧光共聚焦显微镜和光学相干断层扫描，将用于检查不同长度尺度的细胞和细胞外环境。多尺度流变探针，包括由光学镊子操纵的微珠，可变形的微凝胶和油或脂肪滴，将用于绘制亚细胞到多细胞区域的应力-应变场。细胞生长和反应之间的相关性以及应力应变图将指导研究人员开发理论模型以及测试这些模型的有效性。该项目将促进对复杂三维环境中干细胞分化和细胞迁移的机械转导的理解。膜蛋白运输的实验将产生新的数据和实验方法，以发现细胞用于响应血流的机制。这个项目的成功将通过期刊出版物和参与学生在国内和国际会议上的研究报告来评估。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。

The goals of this project are to develop advanced imaging techniques and innovative microscopic probes to determine how biological cells respond to force and to train U.S. students in these techniques. These experiments will help us understand how stem cells differentiate into functional cell types, how cancer cells spread, and how blood flow is regulated. Understanding how cells interact with their environment is essential for developing treatments for a variety of health-related issues, ranging across joint repairs, cancer therapeutics, tissue engineering, and heart and vascular disease prevention and treatment. The scientific goals will be accomplished via a focused international collaboration that provides intensive research training for graduate and undergraduate students. Each year, research will be conducted by 4 - 6 U.S. students working toward their Ph.D. or undergraduate senior thesis under joint supervision of professors from Lehigh University and researchers in the French National Laboratories in the University of Bordeaux, France. Each of the participating students will work in Bordeaux laboratories in the summer and at Lehigh for the rest of the year. Gender balance and race and ethnic diversities will be considered to ensure the development of the United States STEM workforce in a diverse, inclusive and international environment.A team of Lehigh faculty in science and engineering departments in collaboration with CNRS researchers in the University of Bordeaux, France will conduct themed research projects with aims to develop multiscale microrheology to investigate mechanotransduction of multicellular organoids, time-lapse confocal imaging of stem cell differentiation in 3D-printed scaffolds, and magnetic nanoparticle-mediated transport of membrane-bound proteins on a supported membrane. Three model systems are to be developed for such investigation: organelles confined by sub-millimeter hydrogel capsules, 3D printed bio-scaffolds and supported lipid membranes embedded with magnetic nanoparticle-labeled membrane-bound proteins. Multiscale imaging modalities, including fluorescence confocal microscopy and optical coherent tomography, will be used to examine cellular and extracellular milieu at different length scales. Multiscale rheology probes, including microbeads manipulated by optical tweezers, deformable microgels and oil or fat droplets, will be used to map the stress-strain field in subcellular to multicellular domains. Correlation between cellular growth and response and the stress-strain maps will guide the researchers in developing theoretical models as well as testing the validity of these models. This project will advance understanding of mechanotransduction of stem cell differentiation and cell migration in complex three dimensional environments. Experiments on transport of membrane proteins will generate new data and experimental approaches to discover the mechanisms that cells use to respond to blood flow. Success of this project will be assessed by journal publications and by presentations of research by the participating students in national and international conferences.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.