A Photoactivatable α5β1‐Specific Integrin Ligand

• Published in: Chembiochem : a European journal of chemical biology 2018-06, Vol.19 (12), p.1280-1287
• Main Authors: Nair, Roshna V., Farrukh, Aleeza, del Campo, Aránzazu
• Format: Article
• Language: English
• Subjects: Activation; Biological activity; Biomaterials; Biomedical materials; Brain; Brain tumors; cell adhesive ligands; Cell migration; Chemical synthesis; Chromophores; Colon; Exposure; Functional groups; Immobilization; integrin; Integrins; Ligands; Light levels; Lungs; Microenvironments; Organic chemistry; peptidomimetics; phototriggers
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201800180

The integrin α5β1 is overexpressed in colon, breast, ovarian, lung and brain tumours, and has been identified as key component in mechanosensing. In order to study how dynamic changes in α5β1 engagement affect cellular behaviour, photoactivatable derivatives of α5β1‐specific ligands are presented in this article. A photoremovable protecting group (PRPG) was introduced into the ligand structure at a relevant position for integrin recognition. The presence of the chromophore temporarily inhibited ligand bioactivity. Light exposure at a cell‐compatible dose efficiently cleaved the protecting group and restored functionality. The photoactive ligand had an azide end‐functional group for covalent immobilisation onto biomaterials by click chemistry. Selective cell responses (attachment, spreading, migration) to the activated ligand on the surface are achieved by controlled exposure to light, at similar levels to the native ligand. Spatial and temporal control of the cellular response is demonstrated, including the possibility of in situ activation. Photoactivatable integrin‐selective ligands in model microenvironments will allow the study of cellular behaviour in response to changes in the activation of individual integrins as consequence of dynamic variations in matrix composition. Light, integrin, action! A photoactivatable α5β1 integrin ligand allows α5β1‐specific cell responses to biomaterials to be investigated. With cell‐friendly wavelengths and controlled light exposure, cell processes such as attachment, spreading or migration mediated by α5β1 integrin engagement to the surface can be successfully activated in situ.