Shedding new light on cell-matrix interactions: instrumentation development for non-invasive, real-time microscopic elasticity imaging

揭示细胞-基质相互作用的新线索：非侵入性实时显微弹性成像仪器开发

• 批准号: 1455671
• 负责人: Vladislav Yakovlev
• 金额: $ 55.48万
• 依托单位: Texas A&M Engineering Experiment Station
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455671&HistoricalAwards=false
• 关键词: Shedding; new; light; cell; matrix

An award is made to Texas A&M University to develop new instrumentation for a Brillouin imaging system that will measure the elastic properties of cells and extracellular matrix in a 3D cell culture system. Elastic properties of molecular, sub-cellular and cellular structures play a crucial role in many areas of Biology. A prominent example is in embryonic development, where changes in the elastic properties of cells and extracellular matrix contribute to tissue reorganization necessary for organ development. While mechanical interactions between cells and surrounding matrix plays a critical role in many physiological and pathophysiological processes, measurements within 3D tissues have been difficult. Conventional techniques have limited spatial resolution and/or require physical contact with the sample. Brillouin spectroscopy is truly non-invasive and provides information on the elastic properties of biological samples at the subcellular level. While Brillouin spectroscopy has been widely used for elasticity measurements in inorganic materials, the technique has been very slow to catch on in the biological community due to weak signal and difficulty dealing with light scattering. This research project builds upon recent advances in spontaneous and coherent Brillouin scattering microscopies that provide more than three orders of magnitude increase in signal, improving spatial resolution and overcoming strong light scattering. The investigators will apply their optimized Brillouin imaging set-up to characterize dynamic changes in the local mechanical properties of collagen matrices caused by internally generated contractile forces as well as externally applied loads. Imaging the time-varying distribution of stiffness in the matrix will shed new light on the local mechanical environment to which cells ultimately respond to regulate their function. In parallel to these important applications, they aim to develop the next generation nonlinear Brillouin imaging to double spatial resolution and increase temporal resolution by 100-fold.

德克萨斯A M大学获得了一项奖项，为布里渊成像系统开发新的仪器，该系统将测量3D细胞培养系统中细胞和细胞外基质的弹性特性。分子、亚细胞和细胞结构的弹性性质在生物学的许多领域中起着至关重要的作用。一个突出的例子是在胚胎发育中，细胞和细胞外基质的弹性特性的变化有助于器官发育所必需的组织重组。虽然细胞和周围基质之间的机械相互作用在许多生理和病理生理过程中起着关键作用，但3D组织内的测量一直很困难。常规技术具有有限的空间分辨率和/或需要与样品的物理接触。布里渊光谱是真正的非侵入性的，并提供了在亚细胞水平上的生物样品的弹性特性的信息。虽然布里渊光谱已被广泛用于无机材料的弹性测量，但由于信号弱且难以处理光散射，该技术在生物界的流行非常缓慢。该研究项目建立在自发和相干布里渊散射显微镜的最新进展之上，这些显微镜提供了超过三个数量级的信号增加，提高了空间分辨率并克服了强光散射。研究人员将应用其优化的布里渊成像装置来表征由内部产生的收缩力以及外部施加的负载引起的胶原基质局部机械特性的动态变化。对基质中刚度随时间变化的分布进行成像，将为细胞最终响应调节其功能的局部机械环境提供新的线索。在这些重要应用的同时，他们的目标是开发下一代非线性布里渊成像，使空间分辨率提高一倍，时间分辨率提高100倍。