Third Institute of Physics-Biophysics, Georg August University, Göttingen, Germany.
The Rosalind Franklin Institute, Didcot, UK.
Commun Biol. 2024 Nov 30;7(1):1596. doi: 10.1038/s42003-024-07281-4.
Epithelial cadherin (E-cad) mediated cell-cell junctions play a crucial role in the establishment and maintenance of tissues and organs. In this study, we employed metal-induced energy transfer imaging and spectroscopy to investigate variations in intermembrane distance during adhesion between two model membranes adorned with E-cad. By correlating the measured intermembrane distances with the distinct E-cad junction states, we probed the dynamic behavior and diversity of E-cad junctions across different binding pathways. Our observations led to the identification of a transient intermediate state referred to as the X-dimeric state and enabled a detailed analysis of its kinetics. We discovered that the formation of the X-dimer leads to significant membrane displacement, subsequently impacting the formation of other X-dimers. These direct experimental insights into the subtle dynamics of E-cad-modified membranes and the resultant changes in intermembrane distance provide perspectives on the assembly of E-cad junctions between cells. This knowledge enhances our comprehension of tissue and organ development and may serve as a foundation for the development of innovative therapeutic strategies for diseases linked to cell-cell adhesion abnormalities.
上皮钙黏蛋白（E-cad）介导的细胞-细胞连接在组织和器官的建立和维持中起着至关重要的作用。在这项研究中，我们采用金属诱导能量转移成像和光谱技术，研究了两个带有 E-cad 的模型膜之间粘附过程中膜间距离的变化。通过将测量的膜间距离与不同的 E-cad 连接状态相关联，我们探究了不同结合途径下 E-cad 连接的动态行为和多样性。我们的观察结果确定了一种短暂的中间状态，称为 X-二聚体状态，并能够对其动力学进行详细分析。我们发现，X-二聚体的形成会导致膜的显著位移，进而影响其他 X-二聚体的形成。这些对 E-cad 修饰膜的细微动力学和膜间距离变化的直接实验见解，为细胞间 E-cad 连接的组装提供了新的视角。这一知识增进了我们对组织和器官发育的理解，并可能为与细胞-细胞黏附异常相关的疾病的创新治疗策略的发展提供基础。
