State Key Laboratory of Extreme Photonics and Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, Zhejiang 310027, China.
Zhejiang University (ZJU)-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, Zhejiang 311200, China.
Proc Natl Acad Sci U S A. 2024 Oct 15;121(42):e2410688121. doi: 10.1073/pnas.2410688121. Epub 2024 Oct 7.
Cytoskeleton remodeling which generates force and orchestrates signaling and trafficking to govern cell migration remains poorly understood, partly due to a lack of an investigation tool with high system flexibility, spatiotemporal resolution, and computational sensitivity. Herein, we developed a multimodal superresolution imaging system-based architecture-driven quantitative (ADQ) framework in spatiotemporal-angular hyperspace to enable both identification of the optimal imaging mode with well-balanced fidelity and phototoxicity and accurate postcharacterization of microtubule remodeling. In the ADQ framework, a pixel/voxel-wise metric reflecting heterogeneous intertubule alignment was proposed with improved sensitivity over previous efforts and further incorporated with temporal features to map dynamic microtubule rearrangements. The ADQ framework was verified by assessing microtubule remodeling in drug-induced (de)polymerization, lysosome transport, and migration. Different remodeling patterns from two migration modes were successfully revealed by the ADQ framework, with a front-rear polarization for individual directed migration and a contact site-centered polarization for cell-cell interaction-induced migration in an immune response model. Meanwhile, these migration modes were found to have consistent orientation changes, which exhibited the potential of predicting migration trajectory.
细胞骨架重构产生力并协调信号转导和运输，从而控制细胞迁移，但目前对此知之甚少，部分原因是缺乏一种具有高系统灵活性、时空分辨率和计算灵敏度的研究工具。在此，我们开发了一种基于多模态超分辨率成像系统的架构驱动定量（ADQ）框架，在时空角超空间中实现了最佳成像模式的识别，该模式具有良好的保真度和光毒性平衡，并且能够准确地对微管重构进行后特征描述。在 ADQ 框架中，提出了一种像素/体素级别的度量方法，用于反映异质的微管间取向，其灵敏度优于以往的方法，并进一步结合了时间特征来映射动态微管重排。通过评估药物诱导的（解）聚合、溶酶体运输和迁移中的微管重构，验证了 ADQ 框架。ADQ 框架成功揭示了两种迁移模式的不同重构模式，在个体定向迁移中表现为前后极化，在免疫反应模型中细胞-细胞相互作用诱导的迁移中表现为接触点中心极化。同时，发现这些迁移模式具有一致的取向变化，这表明了预测迁移轨迹的潜力。
