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Exogenous Cell Surface Modification with Cell Penetrating Peptide-Conjugated Lipids Causes Spontaneous Cell Adhesion

Year: 2021

Journal: ACS Appl. Bio Mater., Volume 4, MAY 17, page 4598–4606

Authors: Noiri, Makoto; Goto, Yuya; Sato, Yuya; Nakamura, Naoko; Ishihara, Kazuhiko; Teramura, Yuji

Organizations: Bilateral Joint Research Project (Japan-Sweden) of the Japan Society for the Promotion of Science (JSPS); STINT; Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan [26702017, 18KK0305, 19K22951]; Swedish Research Council [2018-04199, 2016-2075-5.1, 2016-04519]; Eurostars-2 joint program [E! 113670]; European Union Horizon 2020 Research and Innovation Program; BPIfrance; German Federal Ministry of Education and Research; VINNOVA; RVO; StemTherapy

Keywords: cell adhesion; PEG-lipid; cell surface modification; cell-penetrating peptide; Tat peptide

The technique of cell patterning on a substrate is of great importance for platforms in cell-based assays. Chemical treatment of the substrate is commonly performed for cell patterning using cationic polymers, extracellular matrices, and antibodies. However, cell patterning could be easier if there is an approach to immobilize cells without treating the substrate surface. We previously reported that cell adhesion could be induced by the modification of the cellular surface with a cell-penetrating peptide (CPP)-conjugated poly(ethylene glycol)-phospholipid (CPP-PEG-lipid). This approach does not require chemical modification of the substrate surface, such as polystyrene or glass, and can be used for the cell patterning of floating cells. Here, we aimed to study the mechanism of induced cell adhesion using a representative CPP, Tat peptide (Tat-PEG-lipid). We found that cell adhesion was induced via electrostatic interactions between the Tat peptide and the substrate surface, which could be induced more efficiently by increasing the molecular weight of PEG together with CPPs but not with cationic peptides. The excluded volume effect between neighboring PEG chains could stretch the cell shape better than PEG with lower molecular weight, allowing the cell to spread firmly. In addition, Tat-PEG-lipid did not activate actin filament formation and did not influence the expression of focal adhesion kinase. Thus, the induced cell adhesion by CPP-PEG-lipid did not affect internal cell signaling.