细胞依靠精确调节脉管系统内的屏障功能来维持生理稳定性并促进必需物质的运输。内皮细胞通过专门的粘附物和紧密连接蛋白复合物来实现这一点，这些复合物控制跨血管床的细胞旁通透性。粘附连接由 VE-钙粘蛋白和相关连环蛋白锚定到肌动蛋白细胞骨架上，介导对屏障完整性至关重要的同质粘附。相比之下，由occludin、claudin和连接粘附分子A组成的紧密连接与闭合小带蛋白相互作用，增强了屏障选择性所必需的细胞间连接。内皮细胞-细胞连接在发育、成熟和重塑过程中表现出动态构象，受局部生化和机械信号的调节。这些结构适应在慢性炎症等疾病中发挥着关键作用，其中连接重塑有助于在从癌症到心血管疾病等疾病中观察到血管通透性增加。相反，大脑微脉管系统的特殊连接排列由于其独特的分子组成和紧密的组织而对治疗药物的输送提出了挑战。本评论探讨了内皮细胞-细胞连接构象的分子机制及其对血管通透性的影响。通过强调量化连接变化和理解机械转导途径的最新进展，我们阐明了细胞接触和血流动力学流动的物理力如何影响连接动力学。

Cells depend on precisely regulating barrier function within the vasculature to maintain physiological stability and facilitate essential substance transport. Endothelial cells achieve this through specialized adherens and tight junction protein complexes, which govern paracellular permeability across vascular beds. Adherens junctions, anchored by VE-cadherin and associated catenins to the actin cytoskeleton, mediate homophilic adhesion crucial for barrier integrity. In contrast, tight junctions composed of occludin, claudin, and junctional adhesion molecule A interact with Zonula Occludens proteins, reinforcing intercellular connections essential for barrier selectivity. Endothelial cell-cell junctions exhibit dynamic conformations during development, maturation, and remodeling, regulated by local biochemical and mechanical cues. These structural adaptations play pivotal roles in disease contexts such as chronic inflammation, where junctional remodeling contributes to increased vascular permeability observed in conditions from cancer to cardiovascular diseases. Conversely, the brain microvasculature's specialized junctional arrangements pose challenges for therapeutic drug delivery due to their unique molecular compositions and tight organization. This commentary explores the molecular mechanisms underlying endothelial cell-cell junction conformations and their implications for vascular permeability. By highlighting recent advances in quantifying junctional changes and understanding mechanotransduction pathways, we elucidate how physical forces from cellular contacts and hemodynamic flow influence junctional dynamics.