Dynamic studies of pore forming toxins using a microfluidic cell array

Systematic studies of pore formation mechanisms of toxins in mammalian cell membranes are critical for understanding infectious disease as well as the biomimetic design of artificial toxins to target cancer cells for lysis. In this paper, dynamic studies of the pore formation mechanism of the bacterial toxin Streptolysin O (SLO) are accomplished by using a microfluidic single cell trapping array. HeLa cells are maintained isolated in hydrodynamic traps while a step concentration of SLO monomers is introduced into the device. Using fluorescent imaging analysis and computational modeling, we attempt to characterize the poration mechanism of the toxin by comparing the results to existing models. We observe that the existing models cannot be completely supported by the experimental data and a hybrid model has been created, involving discrete stochastic reaction kinetics to better explain the variability in the single cell behavior.