The cell interior is a crowded chemical space, which limits the diffusion of molecules and organelles within the cytoplasm, affecting the rates of chemical reactions. We provide insight into the relationship between non-specific intracellular diffusion and cytoskeletal integrity. Quantum dots entered the cell through microinjection and their spatial coordinates were captured by tracking their fluorescence signature as they diffused within the cell cytoplasm. Particle tracking revealed significant enhancement in the mobility of biocompatible quantum dots within fibrosarcoma cells versus their healthy counterparts, fibroblasts, as well as in actin destabilized fibroblasts versus untreated fibroblasts. Analyzing the displacement distributions provided insight into how the heterogeneity of the cell cytoskeleton influences intracellular particle diffusion. We demonstrate that intracellular diffusion of non-specific nanoparticles is enhanced by disrupting the actin network, which has implications for drug delivery efficacy and trafficking.
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The authors gratefully acknowledge our funding sources: ONR Grant N000141410538 (DME), NIH U01 EB016027 (DME), the Provost’s Postdoctoral Fellowship for Academic Diversity (MEG), and URF 4-000002-4820 (DME), which made this work possible. Support was also provided by the NSF PIRE OISE-1545884 (RJC, DME), ACS/PRF 54028-ND7 (RJC, EP), NSF/MWN DMR-1210379 (RJC, EP) and NSF/DMR 1507713 (RJC). The work was performed at and supported by the Nano Bio Interface Center (NBIC) at the University of Pennsylvania through NSF NSEC DMR08-32802, NSF MRI DBI-0721913, and NSF NSEC DMR-0425780.
Electronic Supplementary Information (ESI) available. See DOI: https://doi.org/10.1039/C6SM02464E
Grady, Martha E.; Parrish, Emmabeth; Caporizzo, Matthew A.; Seeger, Sarah C.; Composto, Russell J.; and Eckmann, David M., "Intracellular Nanoparticle Dynamics Affected by Cytoskeletal Integrity" (2017). Mechanical Engineering Faculty Publications. 62.