Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907, United States of America.
Rep Prog Phys. 2024 Mar 4;87(3). doi: 10.1088/1361-6633/ad2229.
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 livingcancer biopsies.
本文综述了利用动态光散射的相干光学技术研究细胞内运输的生物物理学。细胞及其组成部分处于不断运动中，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各种功能和机制。从数十纳米的细胞器尺度向上，活体组织内部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。主动运输可以模拟热布朗运动的随机游走，但均方位移远非热平衡，并且可以通过 Lévy 或分数布朗游走显示异常扩散。尽管细胞和组织的平均各向同性三维环境，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，例如细胞器位移沿细胞骨架轨道持续，或者膜沿细胞表面的法向位移，尽管在三维方向上各向同性取向。相干光散射是一种自然的工具来描述这种组织动力学，因为持续的定向运输会在散射光中引起多普勒频移。来自复杂和动态介质的许多频移部分波相互干扰，产生动态散斑，通过散斑对比成像和波动光谱学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、扩散波光谱学、扩散相关光谱学、差动态显微镜和数字全息术提供了相干检测方法，揭示了细胞内过程。在医疗保健应用中，细胞健康和疾病的改变状态会在散射光的统计波动中留下印记。例如，可以通过测量它们在活体癌症活检的多普勒光谱中诱导的变化来监测医学治疗的效果。
