An Epitope‐Imprinted Biointerface with Dynamic Bioactivity For
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An Epitope-Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell-Biomaterial Interactions Pan, G., Shinde, S., Yeung, S. Y., Jakštaitė, M., Li, Q., Wingren, A. G., & Sellergren, B. (2017). An Epitope- Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell-Biomaterial Interactions. Angewandte Chemie International Edition, 56(50), 15959-15963. https://doi.org/10.1002/anie.201708635 Published in: Angewandte Chemie International Edition Document Version: Publisher's PDF, also known as Version of record Queen's University Belfast - Research Portal: Link to publication record in Queen's University Belfast Research Portal Publisher rights © 2020 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. 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Oct. 2021 Angewandte Communications Chemie International Edition:DOI:10.1002/anie.201708635 Dynamic Biointerfaces Very Important Paper German Edition:DOI:10.1002/ange.201708635 An Epitope-Imprinted Biointerface with DynamicBioactivity for Modulating Cell–Biomaterial Interactions Guoqing Pan,* Sudhirkumar Shinde,Sing YeeYeung,Migle˙ Jaksˇtaite˙,Qianjin Li, Anette Gjçrloff Wingren, and Bçrje Sellergren* Abstract: In this study,anepitope-imprinting strategy was great promise in drug targeting and isolation methods for employed for the dynamic displayofbioactive ligands on therapeutics and diagnostics.[3] amaterial interface.Animprinted surface was initially Current methods to control reversible ligand presentation designed to exhibit specific affinity towardsashort peptide on biomaterial interfaces mainly rely on surface functional- (i.e., the epitope). This surface was subsequently used to ization with reversible linkers (e.g.,noncovalent or reversible anchor an epitope-tagged cell-adhesive peptide ligand (RGD: covalent interactions) to which the bioactive ligand is Arg-Gly-Asp). Owing to reversible epitope-binding affinity, tethered. Forexample,bymeans of host–guest interactions,[4] ligand presentation and thereby cell adhesion could be reversible covalent interactions,[5] molecular assembly,[6] or controlled. As compared to current strategies for the fabrica- other multiple noncovalent interactions,[7] the integrin-tar- tion of dynamic biointerfaces,for example,through reversible geted cell-adhesive peptide RGD (Arg-Gly-Asp)[8] could be covalent or host–guest interactions,such amolecularly tunable dynamically and reversibly immobilized on biointerfaces to dynamic system based on asurface-imprinting process may regulate cell-adhesion behavior. These approaches towards unlock new applications in in situ cell biology,diagnostics,and the simulation of reversible ligand presentation in abiological regenerative medicine. system have greatly promoted the development of dynamic biointerfaces and anew generation of artificial ECM materi- Cellular processes are crucially dependent on dynamic als.Todate,only afew reversible linkage chemistries have receptor–ligand interactions occurring at the interface been exploited. In view of the vast number of natural between the cell membrane and the extracellular matrix receptor–ligand pairs in biology,further effort is warrented. (ECM).[1] Changes in these interactions as aconsequence of Linkages mimicking the exquisite complementarity exhibited ECM remodeling give rise to specific cell-signaling and by natural ligand–receptor pairs are particularly attractive,[9] intracellular cascades.These processes are central to physi- but current strategies in this direction still leave significant ology and pathological processes,such as tissue self-repair room for improvement. and tumorigenesis.[1b,c] As mimics of such dynamic interac- To attain molecularly tunable reversibility in analogy with tions,artificial matrices with the reversible display of natural receptor–ligand interactions we turned to molecular bioactive ligands have attracted much attention. Surfaces imprinting and molecularly imprinted polymers (MIPs).[10] capable of modulating cell–biomaterial interactions are Therecognition sites in MIPs,generally created by atem- commonly exploited for in situ cell-biology experimentation plate-imprinting process,are spatially complementary to the and in tissue engineering.[1c,2] Furthermore,adynamic bio- shape and functionality of the template molecules.[10a–c] Thus, interface with reversibly immobilized ligands has also shown molecular recognition in MIPs occurs by a“lock and key” mechanism similar to natural receptor–ligand interactions.In [*] Prof. Dr.G.Pan, Dr.S.Shinde, S. Y. Yeung, M. Jaksˇtaite˙,Dr. Q. Li, contrast to the scarce number of dynamic covalent or host– Prof. Dr.A.G.Wingren, Prof. Dr.B.Sellergren guest-based linkages,[11] imprinting can be used to tailor Department of Biomedical Sciences reversible affinity towards various ligands,including small Faculty of Health and Society,Malmç University molecules,peptides,and proteins.[12] It has been shown that SE 205 06 Malmç (Sweden) MIPs now can challenge and even exceed the performance of E-mail:[email protected] [email protected] antibodies in affinity related applications both in vitro and in [12a,13] Prof. Dr.G.Pan vivo. To date,however,few attempts have been made to Institute for Advanced Materials use molecular imprinting for the reversible introducation of School of Materials Science and Engineering, Jiangsu University surface bioactivity.[14] Zhenjiang, Jiangsu, 212013 (China) Recently,wedesigned an RGD-peptide-imprintedsub- E-mail:[email protected] strate to assist fast cell-sheet harvesting.[12c] Given that we Supportinginformation and the ORCID identification number(s) for then used bioactive ligands as templates per se in that system, the author(s) of this article can be found under: template binding would produce two counteracting effects: https://doi.org/10.1002/anie.201708635. 1) it would concentrate the bioactive molecules near the 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. interface,and 2) tightly bound bioactive molecules would be KGaA. This is an open access article under the terms of the Creative unaccessible for receptor binding. Commons Attribution-NonCommercial-NoDerivs License, which permitsuse and distribution in any medium, provided the original To address the latter problem, we employed in this study [15] work is properly cited, the use is non-commercial and no modifica- an epitope-imprinting strategy for introducing cell-adhe- tions or adaptations are made. sive RGD in afully exposed form. Theprinciple is based on Angew.Chem. Int.Ed. 2017, 56,15959 –15963 2017 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim 15959 Angewandte Communications Chemie the use of ashort peptide (the epitope) as template during the (DDDGGDDDSSSSSRGDS) consisting of the epitope tag imprinting process and subsequently use of this epitope as an (DDDGGDDD) at the N-terminus,ahydrophilic spacer RGD tag for anchoring the RGD sequence to the substrate (SSSSS) in the middle,and an integrin-targeted peptide surface.Inthis design, the epitope peptide could act as (RGDS) at the C-terminal end, was designed for subsequent areversible anchor of RGD peptide,thus leaving the latter peptide rebinding and cell-recognition experiments.Before exposed for interaction with cell-surface integrin receptors. microcontact imprinting,the epitope template was covalently Moreover,the addition of an appropriate amount of epitope immobilized on acover glass at the C-terminal end (see peptide to the system would induce gradual release of the Figure S1 in the Supporting Information). Theimprinting was bound RGD-based peptides through competitive molecular subsequently performed between the cover glass with the exchange;that is,the bioactivity at the material interface can immobilized epitope and amethacrylate-modified quartz be dynamically controlled. substrate (10 mm in diameter). Thepolymerization reaction To obtain high epitope affinity in the resultant MIPs for was photochemically initiated by aUVlamp after dripping stable RGD anchoring,wefocused on charged peptide 3 mLofaphosphate buffer solution (PBS,0.02m,pH7.4) sequences capable of engaging in multiple ionic interactions containing 1m 2-hydroxyethyl acrylamide (hydrophilic with afunctional monomer.Exploitation of the amidine– backbone monomer), 0.01m 4-acrylamidophenyl(amino)- carboxylate interaction seemed particularly worthwhile given methaniminium chloride (benzamidine-bearing monomer; its high stability in competitive solvents and previous success see Figure S2),[13d] and 0.05m methylenebisacrylamide in molecular imprinting,[16] for example,the use of benzami- (cross-linker) onto the cover glass.Bypolymerization