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

得克萨斯农工大学被授予为布里渊成像系统开发新仪器的奖项，该仪器将在3D细胞培养系统中测量细胞和细胞外基质的弹性属性。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。一个突出的例子是胚胎发育，细胞和细胞外基质弹性性质的变化有助于器官发育所需的组织重组。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学过程中发挥着关键作用，但在3D组织中进行测量一直是困难的。常规技术具有有限的空间分辨率和/或需要与样品进行物理接触。布里渊光谱学是真正的非侵入性的，并在亚细胞水平上提供关于生物样品的弹性性质的信息。虽然布里渊光谱学已被广泛应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，该技术在生物界的普及非常缓慢。这一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的基础上，这些显微镜提供了信号增加三个数量级以上、提高空间分辨率和克服强光散射的能力。研究人员将应用他们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载荷引起的胶原基质局部机械性能的动态变化。想象基质中硬度的时变分布将为细胞最终对其做出反应以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，使空间分辨率翻一番，时间分辨率提高100倍。

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.