Ligand-Receptor Interaction Triggers Hopping and Sliding Motions on Living Cell Membranes.
Ligand-Receptor Interaction Triggers Hopping and Sliding Motions on Living Cell Membranes.
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DOI：
10.1021/jacs.3c06925
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发表时间：
2023-11
影响因子：
15
通讯作者：
Zhongju Ye;Chen Zhang;Jie Yuan;Lehui Xiao
中科院分区：
文献类型：
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作者：
Zhongju Ye;Chen Zhang;Jie Yuan;Lehui Xiao
研究纳米货物在活细胞膜上的表面捕获和释放过程对于理解细胞膜的转运过程至关重要。在这项工作中，我们在商用暗场光学显微镜上实现了全内反射散射（TIRS）照明，而无需引入任何额外的光学元件。通过逐渐减小激发光路中的光阑尺寸，可以很好地控制入射光束的角度。在最佳条件下，激发光可以在玻璃/水界面上完全反射，形成一层薄薄的倏逝场，用于TIRS照明。由于消失场的指数衰减特性，纳米货物沿垂直方向的位移可以在强度轨迹上直接求解。利用这种方法，我们选择性地监测了转铁蛋白修饰的纳米货物在活细胞膜上的动力学。结合位点识别过程涉及局限扩散和远程搜索之间的过渡，表现出非高斯和非遍历的行为。更有趣的是，流体细胞膜上的二维快速滑动和三维跳跃运动也被区分开来，这本质上是由配体-受体相互作用的强度调节的，如自由能谱所示。这些异质和动态的相互作用共同控制了纳米货物在脂质膜上的扩散模式，从而决定了细胞易位效率。
Exploring the surface-capturing and releasing processes of nanocargo on the living cell membrane is critical for understanding the membrane translocation process. In this work, we achieve total internal reflection scattering (TIRS) illumination on a commercial dark-field optical microscope without the introduction of any additional optical components. By gradually reducing the diaphragm size in the excitation light path, the angle of the incident beam can be well manipulated. Under optimal conditions, the excitation light can be totally reflected at the glass/water interface, resulting in a thin layer of evanescent field for TIRS illumination. Due to the exponential decay feature of the evanescent field, the displacement of the nanocargo along the vertical direction can be directly resolved in the intensity track. With this method, we selectively monitor the dynamics of the transferrin-modified nanocargo on the living cell membrane. Transition between confined diffusion and long-range searching is involved in the binding site recognition process, which exhibits non-Gaussian and nonergodic-like behavior. More interestingly, 2D fast sliding and 3D hopping motions are also distinguished on the fluidic cell membrane, which is essentially modulated by the strength of ligand-receptor interactions, as revealed by the free-energy profiles. These heterogeneous and dynamic interactions together control the diffusion mode of the nanocargo on the lipid membrane and, thus, determine the cellular translocation efficiency.