Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid: A New Cell Glue for 3D Cell-Based Structures
Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid: A New Cell Glue for 3D Cell-Based Structures
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DOI：
10.1021/acsami.6b14584
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发表时间：
2017-01-11
影响因子：
9.5
通讯作者：
Nilsson, Bo
中科院分区：
文献类型：
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作者：
Teramura, Yuji;Asif, Sana;Nilsson, Bo
我们合成了一种新的材料，细胞穿透肽共轭聚乙二醇-脂质（CPP-PEG-lipid），它可以诱导漂浮细胞的粘附。通过用CPP-PEG-脂质修饰细胞表面，可以诱导具有铺展的牢固细胞粘附。细胞粘附诱导的CPP，但不是由我们测试的任何其他阳离子短肽。在此，我们使用漂浮细胞系CCRF-CEM以及原代人T细胞、B细胞、红细胞和肝细胞证明了粘附。与悬浮培养的细胞相比，贴壁细胞更快地被诱导附着到具有细胞表面修饰的基底上。附着的关键因素是通过PEG-脂质（PEG > 20 kDa）将CPP定位在细胞膜上。PEG链上的这些阳离子CPP能够与带负电荷的基底表面如聚苯乙烯（PS）表面、玻璃表面和PS微纤维相互作用，诱导牢固的细胞粘附和细胞铺展。此外，与与细胞膜强烈相互作用的正常阳离子肽相反，CPP与细胞表面的相互作用较小，因为它们的细胞穿透性质，使它们更容易将细胞粘附到基底表面。诱导细胞粘附后，未观察到对细胞活力或细胞增殖的影响。通过这种技术，细胞可以很容易地固定在PS微纤维上，这是制造3D细胞结构的重要步骤。固定在3D PS微纤维上的细胞是活的，人肝细胞在微纤维上显示出正常的尿素和白蛋白产生。这种方法在诱导牢固的细胞粘附方面是新颖的-通过一步处理。
We synthesized a novel material, cell-penetrating peptide conjugated poly(ethylene glycol)-lipid (CPP-PEG-lipid), that can induce the adhesion of floating cells. Firm cell adhesion with spreading could be induced by cell surface modification with the CPP-PEG-lipids. Cell adhesion was induced by CPPs but not by any other cationic short peptides we tested. Here, we demonstrated adherence using the floating cell line CCRF-CEM as well as primary human T cells, B cells, erythrocytes, and hepatocytes. As compared to cells grown in suspension, adherent cells were more rapidly induced to attach to substrates with the cell-surface modification. The critical factor for attachment was localization of CPPs at the cell membrane by PEG-lipids with PEG > 20 kDa. These cationic CPPs on PEG chains were able to interact with substrate surfaces such as polystyrene (PS) surfaces, glass surfaces, and PS microfibers that are negatively charged, inducing firm cell adhesion and cell spreading. Also, as opposed to normal cationic peptides that interact strongly with cell membranes, CPPs were less interactive with the cell surfaces because of their cell-penetrating property, making them more available for adhering cells to the substrate surface. No effects on cell viability or cell proliferation were observed after the induction of cell adhesion. With this technique, cells could be easily immobilized onto PS microfibers, an important step in fabricating 3D cell-based structures. Cells immobilized onto 3D PS microfibers were alive, and human hepatocytes showed normal production of urea and albumin on the microfibers. This method is novel in inducing firm cell adhesion-via a one-step treatment.