The influence of tiered layers of surface-grafted poly(ethylene glycol) on receptor-ligand-mediated adhesion between phospholipid monolayer-stabilized microbubbles and coated class beads
The influence of tiered layers of surface-grafted poly(ethylene glycol) on receptor-ligand-mediated adhesion between phospholipid monolayer-stabilized microbubbles and coated class beads
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DOI：
10.1021/la990749r
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发表时间：
2000-03-21
期刊：
影响因子：
3.9
通讯作者：
Needham, D
中科院分区：
文献类型：
--
作者：
Kim, DH;Klibanov, AL;Needham, D
本研究的目的是测量一种典型的磷脂稳定的超声造影剂，其表面已衍生配体分子，和玻璃珠表面涂覆有相应的受体之间的特异性粘附的强度。特别是，检查了表面“结构”（表面接枝分子的尺寸和密度）在介导粘附中的作用。通过改变壳组分的摩尔比[脂质：聚（乙二醇）（PEG）]来改变气泡壳上的配体表面密度。制备过程中的表面活性剂稳定剂：配体-脂质]。测试了两种受体-配体系统：抗生物素蛋白-生物素和抗荧光素-荧光素。中心研究方法是显微操作技术的一种新的应用，其中单个微泡和玻璃珠被捕获由单独的移液管在水性环境中，并使彼此粘合剂接触。微珠移液器施加的抽吸压力逐渐增加，直到施加将微珠从气泡分离所需的力水平。显微操作技术提供的优点是，可以在受控条件下观察到单个粘附事件，并且根据压力和系统几何形状确定实现气泡分离所需的力。粘附的强度被检查作为脂质壳和受体-配体对的组成和结构的函数。表面之间粘附的成功取决于邻近表面PEG的空间位阻的配体的可用性。如果配体通过比PEG稳定剂更长的PEG间隔基连接到壳，则粘附成功;如果配体不在延长的间隔基上，则粘附失败。粘附强度随着配体-脂质浓度的增加而增加并趋于稳定。当设计可靶向稳定的造影剂时，必须考虑这种现象。
The goal of the current study is to measure the strength of specific adhesion between a prototypical phospholipid-stabilized ultrasound contrast agent, the surface of which has been derivatized with a ligand molecule, and a glass bead surface coated with the corresponding receptor. In particular, the role of surface "architecture" (the size and density of surface-grafted molecules) in mediating adhesion is examined, The ligand surface density on bubble shells is varied by changing the mole ratios of shell components [lipid: poly(ethylene glycol) (PEG)ylated surfactant stabilizer:ligand-lipid] during preparation. Two receptor-ligand systems are tested: avidin-biotin and antifluorescein-fluorescein. The central investigative method is a novel application of the micromanipulation technique in which an individual microbubble and a glass bead are captured by separate pipets in an aqueous environment and brought into adhesive contact with each other. Aspiration pressure applied by the bead pipet is incrementally increased until the level of force required to detach the bead from the bubble is exerted. The micromanipulation technique offers the advantage that a single adhesion event can be observed under controlled conditions, and the force required to effect bubble detachment is determined from pressure and system geometry. The strength of adhesion is examined as a function of composition and structure of the lipid shell and the receptor-ligand pair. The success of adhesion between surfaces is dependent on the availability of ligand proximal to the steric barrier of surface PEG. If the ligand is attached to the shell via a PEG spacer longer than that of the PEG stabilizer, then adhesion succeeds; if the ligand is not on an extended spacer, adhesion fails. Adhesion strength increases and plateaus with increasing ligand-lipid concentration. Such phenomena must be considered when engineering a targetable stabilized contrast agent.