This review examines the biological physics of intracellular transport probed by the coherent optics of dynamic light scattering from optically thick living tissues. Cells and their constituents are in constant motion, composed of a broad range of speeds spanning many orders of magnitude that reflect the wide array of functions and mechanisms that maintain cellular health. From the organelle scale of tens of nanometers and upward in size, the motion inside living tissue is actively driven rather than thermal, propelled by the hydrolysis of bioenergetic molecules and the forces of molecular motors. Active transport can mimic the random walks of thermal Brownian motion, but mean-squared displacements are far from thermal equilibrium and can display anomalous diffusion through Lévy or fractional Brownian walks. Despite the average isotropic three-dimensional environment of cells and tissues, active cellular or intracellular transport of single light-scattering objects is often pseudo-one-dimensional, for instance as organelle displacement persists along cytoskeletal tracks or as membranes displace along the normal to cell surfaces, albeit isotropically oriented in three dimensions. Coherent light scattering is a natural tool to characterize such tissue dynamics because persistent directed transport induces Doppler shifts in the scattered light. The many frequency-shifted partial waves from the complex and dynamic media interfere to produce dynamic speckle that reveals tissue-scale processes through speckle contrast imaging and fluctuation spectroscopy. Low-coherence interferometry, dynamic optical coherence tomography, diffusing-wave spectroscopy, diffuse-correlation spectroscopy, differential dynamic microscopy and digital holography offer coherent detection methods that shed light on intracellular processes. In health-care applications, altered states of cellular health and disease display altered cellular motions that imprint on the statistical fluctuations of the scattered light. For instance, the efficacy of medical therapeutics can be monitored by measuring the changes they induce in the Doppler spectra of living ex vivo cancer biopsies.

中文翻译：

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活组织中细胞动力学的相干光散射

这篇综述研究了通过光学厚活体组织动态光散射的相干光学探测的细胞内运输的生物物理学。细胞及其成分处于持续运动中，由跨越多个数量级的广泛速度组成，反映了维持细胞健康的广泛功能和机制。从数十纳米及以上的细胞器尺度来看，活体组织内的运动是主动驱动的，而不是热驱动的，由生物能分子的水解和分子马达的力推动。主动传输可以模拟热布朗运动的随机游走，但均方位移远离热平衡，并且可以通过 Lévy 或分数布朗游走显示异常扩散。尽管细胞和组织具有平均各向同性的三维环境，但单个光散射物体的主动细胞或细胞内运输通常是伪一维的，例如，细胞器位移沿着细胞骨架轨道持续存在，或者膜沿着细胞法向位移表面，尽管在三个维度上各向同性取向。相干光散射是表征这种组织动力学的自然工具，因为持续的定向传输会引起散射光的多普勒频移。来自复杂和动态介质的许多频移部分波发生干涉，产生动态散斑，通过散斑对比成像和波动光谱揭示组织尺度的过程。低相干干涉测量、动态光学相干断层扫描、扩散波光谱、扩散相关光谱、微分动态显微镜和数字全息术提供了相干检测方法，揭示了细胞内的过程。在医疗保健应用中，细胞健康和疾病状态的改变会显示细胞运动的改变，从而影响散射光的统计波动。例如，可以通过测量医学治疗在离体活体癌症活检的多普勒频谱中引起的变化来监测医学治疗的功效。