“…Nanofabricated devices, including nanostraws (1-3), nanowires (4-7), nanoneedles (8)(9)(10)(11)(12), and nanoelectrodes (13)(14)(15)(16)(17)(18)(19)(20)(21)(22), are increasingly being investigated as tools for cellular studies, but these structures do not readily insert through the cell membrane (2)(3)(4)(5)13,23), and assessing when (or whether) penetration has occurred is difficult due to the nanoscale features of the probe-membrane interface. To design cell-penetrating nanoprobes, a systematic approach is needed to describe nanostructure-membrane interactions at relevant temporal and spatial scales, particularly the processes of nanoprobe insertion through (3,(8)(9)(10)(11)(12)(13)15,18,24,25) or fusion with (14,16,19,(26)(27)(28) the plasma membrane.…”