Beales Paul A, Vanderlick T Kyle
Department of Chemical Engineering, Princeton University, Princeton, New Jersey, USA.
Biophys J. 2009 Feb 18;96(4):1554-65. doi: 10.1016/j.bpj.2008.11.027.
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.
我们使用膜锚定DNA作为脂质囊泡之间的模型粘附受体。通过研究将囊泡束缚成超结构的DNA双链体形成的热稳定性，我们表明10碱基DNA序列的解链温度取决于被束缚囊泡的脂质组成。我们提出了一个简单的模型，该模型描述了膜间相互作用如何使DNA结合的自由能景观发生倾斜。从我们的模型中，我们估计了囊泡之间结合位点中每个DNA的面积以及粘附斑的总面积。我们发现，含有少量用膜锚定DNA修饰的阳离子脂质的囊泡可以通过特定的DNA相互作用可逆地束缚，并且DNA还会在这些膜之间诱导出小的吸引力，从而稳定DNA双链体。通过增加结合时的平衡膜间距离，我们表明膜间相互作用对于DNA的结合热力学可忽略不计，因此在足够大的囊泡间距下，囊泡聚集体的热稳定性变得与脂质组成无关。我们讨论了我们的发现对于细胞粘附和融合受体以及通过DNA杂交进行纳米结构材料的可编程自组装的意义。
