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柔性纳米粒子协同内吞的动力学研究
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摘要
内吞是细胞膜摄入外界物质的重要方式,细胞膜通过将外界物质(比如药物)逐渐包覆并内化。目前,人们对于尺寸[1]、形状[2]和表面化学修饰对作为药物载体的纳米颗粒的内吞过程影响关注较多,但是对纳米粒子力学性质对其内吞机制和动力学过程关注较少[3]。最近,我们基于三角网格结构建立了柔性纳米粒子的封闭壳层模型[4](Fig.1),通过体积和表面积约束,纳米粒子可以在保持体积和表面积不变的情况下,与生物膜发生相互作用时发生弹性形变。基于这种方法,我们可以建立具有不同形状的纳米粒子,并研究力学弹性对纳米粒子的细胞内吞机制的影响。在此基础上,我们研究了两个柔性纳米粒子内吞的协同机制(Fig.2)。我们发现两个球形的柔性纳米粒子距离足够接近时,存在一定的几率发生协同内吞过程。内吞开始时,纳米粒子相互贴近并发生形变;然后,生物膜从两端逐渐包覆纳米粒子,并进一步挤压纳米粒子使其贴合更紧密;在纳米粒子继续"下沉"的过程中,中间接触部分受到生物膜挤压而凹陷,形成"哑铃"形状;最后生物膜从两端逐渐完成对纳米粒子的包覆。在该过程中,两个粒子之间的接触面积逐渐增大。对于长椭球和扁椭球形状的柔性纳米粒子,其协同内吞是以较小接触面积的状态完成内吞的(即长椭球的最后状态为"头碰头",扁椭球的最后状态为"肩并肩")。
Endocytosis is the main way of cell to uptake outside materials,and the cell membrane internalizes the materials(e.g.drug) by the way of wrapping.So far,people mainly focus on how nanoparticle's size[1],shape[2] and surface chemical modification influence its endocytic process,but less attention was paid to the effects of mechanical property [3].Recently,we built a model for elastic nanoparticle which is a closed shell being constructedby triangle mesh [4](Fig.1).For this nanoparticle,its volume and surface areaare restrained to keep them unchanged,butcan be deformed elastically when interacts with membrane.Based on this method,we built nanoparticles with different shapes and studied the effects of mechanical elasticity on the endocytosis kinetics of nanoparticle by cell membrane.Based on this model,we studied the endocytosis mechanism of two elastic nanoparticles(Fig.2).We found thatthese two nanoparticles were internalized in a collaborative manner when the distance betweenthem wasshort enough.At beginning,the two nanoparticlesgot in touch with each other and deformed;then membrane wrapped the two nanoparticles from the sides and compressed them to make them tighter fit;during the further"sinking" of nanoparticles,the contact areawas compressed by membrane and the two nanoparticles was observed in a "dumbbell-like"form;at last,the membrane wrapped the nanoparticles gradually from the outer sides,induced the slowly increasing of the contact areaduring this process.For the endocytosis of two prolate or oblate nanoparticles,their contact areas are relatively small when they are wholly wrapped(The final state is "head by head" for prolate nanoparticles,but "shoulder by shoulder" for oblate nanoparticles).
引文
[1]Zhang,S.,Li,J.,Lykotrafitis,G.,Bao,G.,&Suresh,S.Advanced Materials 2009,21(4):419-424.
    [2]Dasgupta,S.,Auth,T.,&Gompper,G.Nano letters 2014,14(2):687-693.
    [3]Yi,X.,Shi,X.,&Gao,H.Physical Review Letter.2011,107(9):098101.
    [4]Pivkin,I.V.,&Karniadakis,G.E.Physical Review Letter.2008,101(11):118105.

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