Binding kinetics of liposome conjugated E-selectin and P-selectin glycoprotein ligand-1 measured with atomic force microscopy.
Binding kinetics of liposome conjugated E-selectin and P-selectin glycoprotein ligand-1 measured with atomic force microscopy.
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DOI：
10.1016/j.colsurfb.2021.112002
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Zhou Y;Cao W;Xu Z;Zhang XF;Liu Y
已经开发了各种配体官能化的脂质体用于靶向治疗。通常，配体和靶蛋白的结合特性用表面等离子体共振（SPR）测量，其中蛋白质固定在刚性表面上。然而，脂质体结合蛋白质和刚性表面结合蛋白质之间的蛋白质-配体结合动力学的差异还没有完全理解。本文利用原子力显微镜（AFM）研究了P-选择素糖蛋白配体-1（PSGL-1）和E-选择素在脂质体和刚性表面上的结合动力学。结果表明，蛋白质在脂质体膜上的取向和扩散可以改变蛋白质-配体相互作用的结合动力学。具体而言，AFM探针结合的E-选择素和玻璃结合的PSGL-1的结合和解离速率常数分别为9.32×104 M-1 s-1和1.54 s-1。而对于脂质体结合的E-选择素和玻璃结合的PSGL-1，动力学常数分别为5.00×107 M-1 s-1和2.76 s-1。因此，与附着在刚性表面相比，当蛋白质附着在脂质体上时，结合亲和力增加了一个数量级（从kd = 16.51 µM到kd = 0.06 µM）。这一结果为进一步设计配体靶向脂质体奠定了基础。
Various ligand-functionalized liposomes have been developed for targeted therapies. Typically, the binding properties of the ligands and targeted proteins are measured with surface plasmon resonance (SPR), where the proteins are immobilized on a rigid surface. However, the difference of protein-ligand binding kinetics between liposome-conjugated protein and rigid surface-conjugated protein is not fully understood. In this work, the binding kinetics of P-selectin glycoprotein ligand-1 (PSGL-1) and E-selectin conjugated on liposome and on rigid surfaces are investigated with Atomic Force Microscopy (AFM). The results suggest that protein orientation and diffusion on liposomal membrane can alter the binding kinetics of the protein-ligand interaction. Specifically, the association and dissociation rate constant of AFM probe-conjugated E-selectin and glass-conjugated PSGL-1 are measured as 9.32×104 M−1s−1 and 1.54 s−1, respectively. While for the liposome-conjugated E-selectin and glass-conjugated PSGL-1, the kinetic constants are measured as 5.00×107 M−1s−1 and 2.76 s−1, respectively. Thus, there is an order’s magnitude increase of binding affinity (from kd = 16.51 µM to kd = 0.06 µM) when protein is attached to liposome compared to attached to a rigid surface. The results might provide better understanding and pave the way for the future design of the ligand-targeted liposomes.
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