论文标题
抗体结合报告细胞膜组织中的空间异质性
Antibody binding reports spatial heterogeneities in cell membrane organization
论文作者
论文摘要
细胞膜糖蛋白和糖脂的空间组织对于介导质膜上配体，受体和大分子的结合至关重要。但是，我们目前没有量化活细胞表面大分子拥挤的空间异质性的方法。在这项工作中，我们结合了实验和模拟，以报告在重构的膜和活细胞膜上与纳米空间分辨率的异质性。通过量化IgG单克隆抗体对工程抗原传感器的有效结合亲和力，我们在拥挤的膜表面几纳米内发现了尖锐的梯度。我们对人类癌细胞的测量支持了这样的假设：筏样膜结构域排除了庞大的膜蛋白和糖蛋白。我们在活细胞膜上量化空间拥挤异质性异质性的高通量方法可能会促进单克隆抗体设计，并提供对质膜生物物理组织的机械理解。
The spatial organization of cell membrane glycoproteins and glycolipids is critical for mediating the binding of ligands, receptors, and macromolecules on the plasma membrane. However, we currently do not have the methods to quantify the spatial heterogeneities of macromolecular crowding on live cell surfaces. In this work, we combine experiment and simulation to report crowding heterogeneities on reconstituted membranes and live cell membranes with nanometer spatial resolution. By quantifying the effective binding affinity of IgG monoclonal antibodies to engineered antigen sensors, we discovered sharp gradients in crowding within a few nanometers of the crowded membrane surface. Our measurements on human cancer cells support the hypothesis that raft-like membrane domains exclude bulky membrane proteins and glycoproteins. Our facile and high-throughput method to quantify spatial crowding heterogeneities on live cell membranes may facilitate monoclonal antibody design and provide a mechanistic understanding of plasma membrane biophysical organization.
