Imaging the elastic properties of cells in 3D environment

本项目旨在利用新型布里渊光学显微镜表征三维细胞培养模型中的细胞内和细胞外力学特性。细胞与其局部微环境之间的生物力学相互作用是细胞功能和系统水平行为的重要调节因子。我们目前关于细胞生物力学的大部分知识来自于对二维单层细胞的研究。虽然3D模型的重要性已经被认识到，但在3D培养中很难测量生物力学参数，特别是弹性模量。目前的标准技术，如原子力显微镜和微流变学，需要样品和探针之间的物理接触，或者仅限于分析样品中随机分布的几个点。该项目将开发和验证布里渊显微镜，并将用于研究与体内自然环境相关的各种实验设置中3D和2D微环境中细胞力学行为的异同。该研究将为细胞微环境的维度如何影响细胞和细胞-基质相互作用提供新的数据启发，并在此过程中为细胞生物力学领域提供一种新的显微镜模式。拟议的研究涉及高度多学科的方法，整合了尖端的光学技术和细胞生物力学，因此将推动工程和生命科学的发展。布里渊细胞显微镜有望在细胞生物力学以外的组织工程和癌症研究等几个研究领域产生更广泛的影响，并具有商业化的潜力。此外，该项目为在哈佛医学院和麻省理工学院高度跨学科的环境中教育和培养工程和生命科学之间的研究生和博士后研究人员提供了一个极好的机会。参加哈佛-麻省理工学院生物医学光学暑期研究所和其他暑期实习项目的本科生将有机会为这个项目做出贡献。

PI: YunProposal ID: 1264356This project aims at characterizing both intracellular and extracellular mechanical properties in 3D cell culture models using novel Brillouin optical microscopy. The biomechanical interaction between cells and their local microenvironment is a crucial regulator of cell function and system level behavior. Most of our current knowledge concerning cell biomechanics came from the studies of 2D monolayers. Although the importance of 3D models have been recognized, it has been difficult to measure the biomechanical parameters, particularly the modulus of elasticity, in 3D cultures. Current standard technologies, such as atomic force microscopy and microrheology, require physical contact between a sample and a probe or are limited to the analysis of few points randomly distributed within a sample. This project will develop and validate Brillouin microscopy and will be used to investigate the differences and similarities in cell mechanical behavior between 3D and 2D microenvironments in various experimental settings relevant to the natural environments in vivo. This study will provide new data-inspired insights into how the dimensionality of cellular microenvironment affects the cells and cell-matrix interactions, and in the process, it will make a novel microscopy modality available in the field of cell biomechanics. The proposed research involves highly multidisciplinary approaches integrating the cutting edge optical technology and cellular biomechanics and, therefore, will advance both engineering and life sciences. Brillouin cell microscopy is expected to have broader impacts on several research areas, such as tissue engineering and cancer research, beyond cell biomechanics and has the potential for commercialization. Furthermore, this project provides an excellent opportunity to educate and train graduate students and postdoctoral researchers at the interface between engineering and life sciences in a highly interdisciplinary environment at Harvard Medical School and Massachusetts Institute of Technology. Undergraduate students enrolled in the Harvard-MIT Summer Institute for Biomedical Optics and other summer internship programs will be given the opportunity to contribute to this project.