Combinatorial in Vitro and in Silico Approach To Describe Shear-Force Dependent Uptake of Nanoparticles in Microfluidic Vascular Models

In the present work, we combine experimental and computational methods to define the critical shear stress as an alternative parameter for nanotoxicological and nanomedical evaluations using an in vitro microfluidic vascular model. We demonstrate that our complementary in vitro and in silico approach is well suited to assess the fluid flow velocity above which clathrin-mediated (active) nanoparticle uptake per cell decreases drastically although higher numbers of nanoparticles per cell are introduced. Results of our study revealed a critical shear stress of 1.8 dyn/cm 2 , where maximum active cellular nanoparticle uptake took place, followed by a 70% decrease in uptake of 249 nm nanoparticles at 10 dyn/cm 2 , respectively. The observed nonlinear relationship between flow velocity and nanoparticle uptake strongly suggests that fluid mechanical forces also need to be considered in order to predict potential in vivo distribution, bioaccumulation, and clearance of nanomaterials and novel nanodrugs.