Geneless optical control of cell redox balance in HL-1 cardiac muscle cells

Abstract

Photoactivation of conjugated polymers has been shown to be an attractive approach to modulate biological functions in several cell models; it is characterized by minimal invasiveness, high modulability, spatial selectivity at the level of single cells and even intracellular compartments. Reactive oxygen species produced by polymer photostimulation, in particular, were reported to trigger cell proliferation and recently proposed to finely modulate the cell cycle. Light-activated proliferation is extremely attractive for cardiac muscle cells, to overcome pathological conditions as heart failure and cardiovascular diseases with minimal invasiveness.Here, we specifically address the target to optically modulate the cell redox balance of HL-1 cells, a cardiac muscle cell model, by localized photoexcitation of a light sensitive polymer, namely poly-3-hexyl-thiophene. Scanning electrochemical microscopy is employed to quantify the changes of the cellular redox balance. Both extracellular and intracellular production of reactive oxygen species upon illumination is investigated, by employing poly-3-hexyl-thiophene respectively in the form of thin films or nanoparticles. Our results show that light induced, spatially controlled production of reactive oxygen species by poly-3-hexyl-thiophene films in the extracellular compartment determines the shift of HL-1 redox balance towards more reducing values. Thus, highly resolved spatial control of the illuminated area enables modulation of HL-1 redox balance at the single cell level. The effect on cell redox balance of cytosol internalized poly-3-hexyl-thiophene nanoparticles is also presented.Our work shows that photostimulation of conjugated polymers can be employed as a wireless, geneless technique to modulate on demand the intracellular redox balance, with high spatial resolution and minimal invasiveness, in a biologically relevant model of contractile, functioning cardiomyocytes. In perspective, this approach may be easily extended to other cell systems, wherever a fine control of the cell redox state is desirable, and open the path to innovative therapeutic tools.