The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale.
The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale.
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紧密接触的成本：在纳米尺度上可视化细胞接触的能量景观。
DOI：
10.1016/j.bpj.2020.01.019
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发表时间：
2020
影响因子：
3.4
通讯作者：
Kulenkampff K
中科院分区：
文献类型：
--
作者：
Kulenkampff K
细胞间的接触通常是细胞间信号传递的基础。对于免疫学，T细胞受体与抗原呈递pMHC的结合启动下游信号传导和免疫应答。虽然这种接触是由两个细胞上的蛋白质介导的，产生通常约14 nm的间隙尺寸的界面，但关于接触对参数的影响，例如结合动力学，空间分布和接触内信号蛋白的扩散，已经进行了许多经常相互矛盾的观察。了解探针在这个拥挤的环境中的基本物理约束将有助于为突触中相关蛋白质的信号传导的结合动力学和动力学研究提供信息。通过长时间跟踪不同尺寸的量子点，我们已经证明，有可能获得分子进入接触的概率，进入时扩散的变化，以及接触中粘附蛋白密度的空间异质性的影响。通过分析由T细胞与锚定到支持的脂质双层的粘附蛋白相互作用形成的接触，我们发现，探针被排除在接触条目中的大小依赖性的方式为4.1 nm的间隙探针的差异。我们还观察到探针被困在接触和减少高达85%的扩散密集的粘附蛋白接触。这种方法提供了新的，据我们所知，深入了解细胞-细胞接触的性质，揭示了细胞接触是高度异质性的，因为地形和蛋白质密度相关的过程。这些效应可能会深刻影响细胞之间的信号传导。
Cell-cell contacts often underpin signaling between cells. For immunology, the binding of a T cell receptor to an antigen-presenting pMHC initiates downstream signaling and an immune response. Although this contact is mediated by proteins on both cells creating interfaces with gap sizes typically around 14 nm, many, often contradictory observations have been made regarding the influence of the contact on parameters such as the binding kinetics, spatial distribution, and diffusion of signaling proteins within the contact. Understanding the basic physical constraints on probes inside this crowded environment will help inform studies on binding kinetics and dynamics of signaling of relevant proteins in the synapse. By tracking quantum dots of different dimensions for extended periods of time, we have shown that it is possible to obtain the probability of a molecule entering the contact, the change in its diffusion upon entry, and the impact of spatial heterogeneity of adhesion protein density in the contact. By analyzing the contacts formed by a T cell interacting with adhesion proteins anchored to a supported lipid bilayer, we find that probes are excluded from contact entry in a size-dependent manner for gap-to-probe differences of 4.1 nm. We also observed probes being trapped inside the contact and a decrease in diffusion of up to 85% in dense adhesion protein contacts. This approach provides new, to our knowledge, insights into the nature of cell-cell contacts, revealing that cell contacts are highly heterogeneous because of topography- and protein-density-related processes. These effects are likely to profoundly influence signaling between cells.