DNA as Membrane-Bound Ligand-Receptor Pairs: Duplex Stability Is Tuned by Intermembrane Forces

DNA as Membrane-Bound Ligand-Receptor Pairs: Duplex Stability Is Tuned by Intermembrane Forces
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DOI:
10.1016/j.bpj.2008.11.027
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发表时间:
2009-02-18
影响因子:
3.4
通讯作者:
Vanderlick, T. Kyle
Vanderlick, T. Kyle
中科院分区:
生物学3区
文献类型:
--
作者:
Beales, Paul A.;Vanderlick, T. Kyle

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我们使用膜锚定的DNA作为模型之间的粘附受体脂质囊泡。通过研究DNA双链体形成的热稳定性,它将囊泡束缚成超结构,我们表明,10个碱基的DNA序列的熔化温度取决于束缚囊泡的脂质组成。我们提出了一个简单的模型,描述了膜间相互作用如何倾斜的DNA结合的自由能景观。从我们的模型中,我们估计了囊泡之间的结合位点中每个DNA的面积以及粘附斑块的总面积。我们发现,含有一小部分的阳离子脂质修饰的膜锚定的DNA的囊泡可以通过特定的DNA相互作用可逆地拴系,并且DNA也诱导这些膜之间的小吸引力,这稳定了DNA双链体。通过增加结合的平衡膜间距离,我们表明,膜间相互作用变得可以忽略不计的DNA的结合热力学,因此囊泡聚集体的热稳定性变得独立于脂质组合物在足够大的囊泡间分离。我们讨论了我们的研究结果与细胞粘附和融合受体方面的影响,和可编程的自组装的纳米结构材料的DNA杂交。
We use membrane-anchored DNA as model adhesion receptors between lipid vesicles. By studying the thermal stability of DNA duplex formation, which tethers the vesicles into superstructures, we show that the melting temperature of a 10-base DNA sequence is dependent on the lipid composition of the tethered vesicles. We propose a simple model that describes how the intermembrane interactions tilt the free energy landscape for DNA binding. From our model, we estimate the area per DNA in the binding sites between vesicles and also the total area of the adhesion plaques. We find that vesicles containing a small proportion of cationic lipid that are modified with membrane-anchored DNA can be reversibly tethered by specific DNA interactions and that the DNA also induces a small attraction between these membranes, which stabilizes the DNA duplex. By increasing the equilibrium intermembrane distance on binding, we show that intermembrane interactions become negligible for the binding thermodynamics of the DNA and hence the thermal stability of vesicle aggregates becomes independent of lipid composition at large enough intervesicle separations. We discuss the implications of our findings with regards to cell adhesion and fusion receptors, and the programmable self-assembly of nano-structured materials by DNA hybridization.