Almqvist N, Bhatia R, Primbs G, Desai N, Banerjee S, Lal R
Department of Applied Physics & Mechanical Engineering, Luleå University of Technology, Luleå, Sweden.
Biophys J. 2004 Mar;86(3):1753-62. doi: 10.1016/S0006-3495(04)74243-5.
Cell surface macromolecules such as receptors and ion channels serve as the interface link between the cytoplasm and the extracellular region. Their density, distribution, and clustering are key spatial features influencing effective and proper physical and biochemical cellular responses to many regulatory signals. In this study, the effect of plasma-membrane receptor clustering on local cell mechanics was obtained from maps of interaction forces between antibody-conjugated atomic force microscope tips and a specific receptor, a vascular endothelial growth factor (VEGF) receptor. The technique allows simultaneous measurement of the real-time motion of specific macromolecules and their effect on local rheological properties like elasticity. The clustering was stimulated by online additions of VEGF, or antibody against VEGF receptors. VEGF receptors are found to concentrate toward the cell boundaries and cluster rapidly after the online additions commence. Elasticity of regions under the clusters is found to change remarkably, with order-of-magnitude stiffness reductions and fluidity increases. The local stiffness reductions are nearly proportional to receptor density and, being concentrated near the cell edges, provide a mechanism for cell growth and angiogenesis.
细胞表面的大分子，如受体和离子通道，充当细胞质与细胞外区域之间的界面连接。它们的密度、分布和聚集是影响细胞对许多调节信号做出有效且适当的物理和生化反应的关键空间特征。在本研究中，通过抗体偶联原子力显微镜探针与特定受体——血管内皮生长因子（VEGF）受体之间的相互作用力图谱，获得了质膜受体聚集对局部细胞力学的影响。该技术能够同时测量特定大分子的实时运动及其对局部流变学性质（如弹性）的影响。通过在线添加VEGF或抗VEGF受体抗体来刺激聚集。发现VEGF受体在线添加开始后会向细胞边界集中并迅速聚集。聚集区域的弹性发生显著变化，刚度降低几个数量级，流动性增加。局部刚度降低几乎与受体密度成正比，且集中在细胞边缘附近，为细胞生长和血管生成提供了一种机制。
