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Step-wise linking of vesicles by combining reversible and irreversible linkers - towards total control on vesicle aggregate sizes.
Soft Matter ( IF 2.9 ) Pub Date : 2020-06-26 , DOI: 10.1039/d0sm00995d
N de Lange 1 , F A M Leermakers 1 , J M Kleijn 1
Affiliation  

Small vesicle aggregates as a model for primitive cellular assemblies or for application as multi-compartment drug delivery systems recently received a lot of interest, yet controlling the aggregation of vesicles to predetermined aggregate sizes remains quite a challenge. We show that this type of control is possible by using a combination of two different linker systems: streptavidin–biotin and C18-pNIPAm. The latter linker is a thermoresponsive surfactant, which below its lower critical solution temperature (LCST) of 32 °C acts as barrier on the outside of the vesicles preventing aggregation, even in the presence of other linkers. Above the LCST however, C18-pNIPAm collapses, becomes sticky and thus acts as a linker inducing aggregation. By working at low vesicle concentrations and tuning the C18-pNIPAm/lipid ratio, the aggregation is by design limited. When the temperature drops below the LCST again, the aggregation is reversed. However, this is not the case if other linkers are present. The collapse of C18-pNIPAm above the LCST provides close contact between vesicles, allowing other linker molecules to connect them. By combining the reversible 'switch-like' aggregation properties of C18-pNIPAm, with the irreversible linkage between biotinylated lipids and streptavidin, it is possible to control the size of the aggregates step by step using a simple temperature program.

中文翻译:

通过将可逆和不可逆的连接子结合起来逐步连接囊泡,从而完全控制囊泡聚集体的大小。

小囊泡聚集体作为原始细胞组装的模型或作为多室药物递送系统的应用近来引起了人们的极大兴趣,但是将囊泡聚集控制为预定的聚集体尺寸仍然是一个挑战。我们证明,通过使用两种不同的接头系统:链霉亲和素-生物素和C18-pNIPAm,可以实现这种控制。后者是一种热响应性表面活性剂,即使在存在其他连接剂的情况下,其在低于其较低的临界溶液温度(LCST)32°C时,也可在囊泡外部充当屏障,防止聚集。然而,在LCST上方,C18-pNIPAm折叠,变粘,因此充当诱导聚集的连接子。通过在低囊泡浓度下工作并调节C18-pNIPAm /脂质比,聚合是设计使然。当温度再次降至LCST以下时,聚集逆转。但是,如果存在其他链接器,则不是这种情况。LCST上方C18-pNIPAm的崩溃提供了小泡之间的紧密接触,从而允许其他接头分子将它们连接起来。通过将C18-pNIPAm的可逆“开关样”聚集特性与生物素化脂质和链霉亲和素之间的不可逆键结合起来,可以使用简单的温度程序逐步控制聚集体的大小。
更新日期:2020-07-29
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