Conjugated polymers mediate intracellular Ca2+ signals in circulating endothelial colony forming cells through the reactive oxygen species-dependent activation of Transient Receptor Potential Vanilloid 1 (TRPV1)

• Published in: Cell calcium (Edinburgh) Vol. 101; p. 102502
• Main Authors: Negri, Sharon, Faris, Pawan, Tullii, Gabriele, Vismara, Mauro, Pellegata, Alessandro F., Lodola, Francesco, Guidetti, Gianni, Rosti, Vittorio, Antognazza, Maria Rosa, Moccia, Francesco
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-01-2022
• Subjects: Conjugated polymers; Endothelial colony forming cells; Optical stimulation; Reactive oxygen species; Transient receptor potential vanilloid 1; Optical stimulation; Transient receptor potential vanilloid 1; Conjugated polymers; Reactive oxygen species; Endothelial colony forming cells
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2021.102502

•Optical excitation of rr-P3HT thin films induces a long-lasting increase in [Ca2+]i in circulating endothelial colony forming cells (ECFCs).•The Ca2+ response to light is triggered by TRPV1 and requires the engagement of InsP3 receptors and store-operated Ca2+ entry.•TRPV1 is gated by hydrogen peroxide produced at the interface between the cell membrane and photosensitive nanomaterial upon light stimulation.•TRPV1 may serve as a decoder at the interface between rr-P3HT thin films and ECFCs to translate optical excitation in pro-angiogenic Ca2+ signals.
Endothelial colony forming cells (ECFCs) represent the most suitable cellular substrate to induce revascularization of ischemic tissues. Recently, optical excitation of the light-sensitive conjugated polymer, regioregular Poly (3-hexyl-thiophene), rr-P3HT, was found to stimulate ECFC proliferation and tube formation by activating the non-selective cation channel, Transient Receptor Potential Vanilloid 1 (TRPV1). Herein, we adopted a multidisciplinary approach, ranging from intracellular Ca2+ imaging to pharmacological manipulation and genetic suppression of TRPV1 expression, to investigate the effects of photoexcitation on intracellular Ca2+ concentration ([Ca2+]i) in circulating ECFCs plated on rr-P3HT thin films. Polymer-mediated optical excitation induced a long-lasting increase in [Ca2+]i that could display an oscillatory pattern at shorter light stimuli. Pharmacological and genetic manipulation revealed that the Ca2+ response to light was triggered by extracellular Ca2+ entry through TRPV1, whose activation required the production of reactive oxygen species at the interface between rr-P3HT and the cell membrane. Light-induced TRPV1-mediated Ca2+ entry was able to evoke intracellular Ca2+ release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors, followed by store-operated Ca2+ entry on the plasma membrane. These data show that TRPV1 may serve as a decoder at the interface between rr-P3HT thin films and ECFCs to translate optical excitation in pro-angiogenic Ca2+ signals.
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