Magnetic nanoparticle–mediated massively parallel mechanical modulation of single-cell behavior

Abstract
Cells are dosed with magnetic nanoparticles and patterned onto micromagnetic substrates, enabling the application of controlled and variable mechanical force to tens of thousands of cells. We report a technique for generating controllable, time-varying and localizable forces on arrays of cells in a massively parallel fashion. To achieve this, we grow magnetic nanoparticle–dosed cells in defined patterns on micromagnetic substrates. By manipulating and coalescing nanoparticles within cells, we apply localized nanoparticle-mediated forces approaching cellular yield tensions on the cortex of HeLa cells. We observed highly coordinated responses in cellular behavior, including the p21-activated kinase–dependent generation of active, leading edge–type filopodia and biasing of the metaphase plate during mitosis. The large sample size and rapid sample generation inherent to this approach allow the analysis of cells at an unprecedented rate: in a single experiment, potentially tens of thousands of cells can be stimulated for high statistical accuracy in measurements. This technique shows promise as a tool for both cell analysis and control.