Delivering compounds into cells is a ubiquitous requirement for fundamental life science research
and cell-based clinical applications. Since cells are protected from the outside world by their plasma
membrane, it requires sophisticated technology to deliver compounds across this barrier without
causing toxicity. Photoporation is emerging as a powerful technology to achieve exactly this. It relies
on laser illumination of plasmonic nanoparticles that have been added to cells. Absorption of the
laser energy by the nanoparticles causes the plasma membrane to become permeable by local
heating or pressure effects, allowing external compounds to diffuse into the cells. While it has been
amply demonstrated that photoporation does not cause acute cytotoxicity, it remains unknown how
it affects cell physiology at the short and longer term. Yet, this information is crucial to safely
implement the technology in different settings. Therefore, we will unravel the cellular response to
photoporation. We will thereby analyse early downstream events such as the activation of
membrane repair pathways and induction of cellular stress levels, as well as more persistent
changes in gene expression and genome integrity. The fundamental insights from these studies will
provide a solid basis for making photoporation a standard transfection technology that can be used
with confidence. At the same time, it will help devise strategies to reduce or exploit potential side
effects of photoporation.