Scanning ion conductance microscopy for living cell nanomechanics: principles, advances and applications

Scanning ion conductance microscopy (SICM) has emerged as a high-resolution, non-invasive scanning probe technique for studying living cells under physiological conditions and keeping cells intact during measurements using a nanosize-tip glass pipette. Recent advances have established SICM as a universal platform for quantifying the mechanical properties of single living cells, which are increasingly recognized as crucial for cell function and disease progression. Two approaches, based on active pressure-induced deformation or intrinsic cellular forces, offer a tunable indentation force and spatial resolution. SICM can map the mechanical properties of living cells with high resolution and perform combined imaging with other methods such as confocal microscopy or traction force microscopy. SICM has its niche in drug in vitro efficacy monitoring; it gives unique insights into nanobiomechanics of tumor, blood, neuronal and muscle cells and 3D organoids. SICM is poised to become an acute tool for mechanobiology and drug efficacy studies at the nanoscale.