title: Multi-resolution 3D visualization of the early stages of cellular uptake of peptide-coated nanoparticles.
abstract: A detailed understanding of the cellular uptake process is essential to the development of cellular delivery strategies and to the study of viral trafficking. However, visualization of the entire process, encompassing the fast dynamics (local to the freely diffusing nanoparticle) as well the state of the larger-scale cellular environment, remains challenging. Here, we introduce a three-dimensional multi-resolution method to capture, in real time, the transient events leading to cellular binding and uptake of peptide (HIV1-Tat)-modified nanoparticles. Applying this new method to observe the landing of nanoparticles on the cellular contour in three dimensions revealed long-range deceleration of the delivery particle, possibly due to interactions with cellular receptors. Furthermore, by using the nanoparticle as a nanoscale 'dynamics pen', we discovered an unexpected correlation between small membrane terrain structures and local nanoparticle dynamics. This approach could help to reveal the hidden mechanistic steps in a variety of multiscale processes.
authors.affiliation: Chemistry Department, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Welsher
authors.affiliation: Chemistry Department, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Haw
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008853:Microscopy / Q000379:methods; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000032:analysis / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000032:analysis / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus