title: Bioorthogonal Click Chemistry-Based Synthetic Cell Glue.
abstract: Artificial methods of cell adhesion can be effective in building functional cell complexes in vitro, but methods for in vivo use are currently lacking. Here, a chemical cell glue based on bioorthogonal click chemistry with high stability and robustness is introduced. Tetrazine (Tz) and trans-cyclooctene (TCO) conjugated to the cell surface form covalent bonds between cells within 10 min in aqueous conditions. Glued, homogeneous, or heterogeneous cell pairs remain viable and stably attached in a microfluidic flow channel at a shear stress of 20 dyn cm(-2) . Upon intravenous injection of assembled Jurkat T cells into live mice, fluorescence microscopy shows the trafficking of cell pairs in circulation and their infiltration into lung tissues. These results demonstrate the promising potential of chemically glued cell pairs for various applications ranging from delivering therapeutic cells to studying cell-cell interactions in vivo.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA.
authors.forename: Heebeom
authors.initials: H
authors.lastname: Koo
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA.|Department of Global Biomedical Engineering, Center for Neuroscience and Imaging Research, Sungkyunkwan University, Institute for Basic Science, Suwon, Gyeong Gi-Do, 440-746, South Korea.
authors.forename: Myunghwan
authors.initials: M
authors.lastname: Choi
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.|Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, South Korea.
authors.forename: Eunha
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology, Kyungbuk, 790-784, South Korea.
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Yun
mesh_terms: D000269:Adhesives / Q000494:pharmacology*; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival; D057930:Click Chemistry / Q000379:methods*; D005434:Flow Cytometry; D057166:High-Throughput Screening Assays; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D060847:Metabolic Engineering; D051379:Mice; D008810:Mice, Inbred C57BL; D044085:Microfluidics; D041681:NIH 3T3 Cells
chemical_list: D000269:Adhesives; D007376:Interleukin-2
keywords: cell adhesion; cell delivery; click chemistry; metabolic glycoengineering; tissue engineering