The cellular response to plasma membrane disruption for nanomaterial delivery

Delivery of nanomaterials into cells is of interest for fundamental cell biological research as well as for therapeutic and diagnostic purposes. One way of doing so is by physically disrupting the plasma membrane (PM). Several methods that exploit electrical, mechanical or optical cues have been conceived to temporarily disrupt the PM for intracellular delivery, with variable effects on cell viability. However, apart from acute cytotoxicity, subtler effects on cell physiology may occur as well. Their nature and timing vary with the severity of the insult and the efficiency of repair, but some may provoke permanent phenotypic alterations. With the growing palette of nanoscale delivery methods and applications, comes a need for an in-depth understanding of this cellular response. In this review, we summarize current knowledge about the chronology of cellular events that take place upon PM injury inflicted by different delivery methods. We also elaborate on their significance for cell homeostasis and cell fate. Based on the crucial nodes that govern cell fitness and functionality, we give directions for fine-tuning nano-delivery conditions.