한빛사 논문
Yuri Kim,†,⊥ Hee Joon Jung,∥,#,¶,⊥ Yunjung Lee,‡,§ Sagang Koo,‡,§ Ramar Thangam,† Woo Young Jang,Δ Seong Yeol Kim,† Sangwoo Park,† Sungkyu Lee,† Gunhyu Bae,† Kapil Dev Patel,† Qiang Wei,⌠ Ki-Bum Lee,◁ Ramasamy Paulmurugan,^,◊ Woong Kyo Jeong,Δ Taeghwan Hyeon,‡,§ Dokyoon Kim,‡,o,* Heemin Kang†,▷,*
†Department of Materials Science and Engineering, Korea University, Seoul 02841, Republic of Korea.
‡Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea.
§School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea.
∥Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA 60208.
#International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA 60208.
¶NUANCE Center, Northwestern University, Evanston, IL, USA 60208.
ΔDepartment of Orthopedic Surgery, Korea University Anam Hospital, Seoul 02841, Republic of Korea.
⌠College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, Chengdu 610065, China.
◁Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, USA 08854.
^Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford University, Palo Alto, CA, USA 94304.
◊Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Stanford University, Palo Alto, CA, USA 94304.
oDepartment of Bionano Engineering and Bionanotechnology, Hanyang University, Ansan 15588, Republic of Korea.
▷Department of Biomicrosystem Technology, Korea University, Seoul 02841, Republic of Korea.
Y.K. and H.J.J. contributed equally to this work.
*Corresponding author.
Abstract
The receptor–ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor magnetic nanoparticle aggregates of tunable sizes over the cell-adhesive RGD ligand (Arg-Gly-Asp)-active material surface while maintaining the density of dispersed ligands accessible to macrophages at constant. Lowering the accessible ligand dispersity by increasing the aggregate size at constant accessible ligand density facilitates the binding of integrin receptors to the accessible ligands, which promotes the adhesion of macrophages. In high ligand dispersity, distant magnetic manipulation to lift the aggregates (which increases ligand accessibility) stimulates the binding of integrin receptors to the accessible ligands available under the aggregates to augment macrophage adhesion-mediated pro-healing polarization both in vitro and in vivo. In low ligand dispersity, distant control to drop the aggregates (which decreases ligand accessibility) repels integrin receptors away from the aggregates, thereby suppressing integrin receptor–ligand binding and macrophage adhesion, which promotes inflammatory polarization. Here, we present “accessible ligand dispersity” as a novel fundamental parameter that regulates receptor–ligand binding, which can be reversibly manipulated by increasing and decreasing the ligand accessibility. Limitless tuning of nanoparticle aggregate dimensions and morphology can offer further insight into the regulation of receptor–ligand binding in host cells.
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