Abstract
Our understanding of the complex cell entry pathways would greatly benefit from a comprehensive characterization of key proteins involved in this dynamic process. Here we devise a novel proteomic strategy named TITAN (Tracing Internalization and TrAfficking of Nanomaterials) to reveal real-time protein-dendrimer interactions using a systems biology approach. Dendrimers functionalized with photoreactive cross-linkers were internalized by HeLa cells and irradiated at set time intervals, then isolated and subjected to quantitative proteomics. In total, 809 interacting proteins cross-linked with dendrimers were determined by TITAN in a detailed temporal manner during dendrimer internalization, traceable to at least two major endocytic mechanisms, clathrin-mediated and caveolar/raft-mediated endocytosis. The direct involvement of the two pathways was further established by the inhibitory effect of dynasore on dendrimer uptake and changes in temporal profiles of key proteins.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12772-12775 |
| Number of pages | 4 |
| Journal | Journal of the American Chemical Society |
| Volume | 137 |
| Issue number | 40 |
| DOIs | |
| State | Published - Oct 14 2015 |
Bibliographical note
Publisher Copyright:© 2015 American Chemical Society.