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Nanoscale Heterogeneities Drive Enhanced Binding and Anomalous Diffusion of Nanoparticles in Model Biomembranes
journal contribution
posted on 2018-01-10, 00:00 authored by Roobala Chelladurai, Koushik Debnath, Nikhil R. Jana, Jaydeep Kumar BasuInteraction
of functional nanoparticles with cells and model biomembranes
has been widely studied to evaluate the effectiveness of the particles
as potential drug delivery vehicles and bioimaging labels as well
as in understanding nanoparticle cytotoxicity effects. Charged nanoparticles,
in particular, with tunable surface charge have been found to be effective
in targeting cellular membranes as well as the subcellular matrix.
However, a microscopic understanding of the underlying physical principles
that govern nanoparticle binding, uptake, or diffusion on cells is
lacking. Here, we report the first experimental studies of nanoparticle
diffusion on model biomembranes and correlate this to the existence
of nanoscale dynamics and structural heterogeneities using super-resolution
stimulated emission depletion (STED) microscopy. Using confocal and
STED microscopy coupled with fluorescence correlation spectroscopy
(FCS), we provide novel insight on why these nanoparticles show enhanced
binding on two-component lipid bilayers as compared to single-component
membranes and how binding and diffusion is correlated to subdiffraction
nanoscale dynamics and structure. The enhanced binding is also dictated,
in part, by the presence of structural and dynamic heterogeneity,
as revealed by STED-FCS studies, which could potentially be used to
understand enhanced nanoparticle binding in raft-like domains in cell
membranes. In addition, we also observe a clear correlation between
the enhanced nanoparticle diffusion on membranes and the extent of
membrane penetration by the nanoparticles. Our results not only have
a significant impact on our understanding of nanoparticle binding
and uptake as well as diffusion in cell and biomembranes, but have
very strong implications for uptake mechanisms and diffusion of other
biomolecules, like proteins on cell membranes and their connections
to functional membrane nanoscale platform.
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Keywords
fluorescence correlation spectroscopynanoparticle bindingsubdiffraction nanoscale dynamicsModel Biomembranes Interactionmembrane nanoscale platformSTED-FCSdrug delivery vehiclesunderstanding nanoparticle cytotoxicity effectsnanoparticle diffusionFCSmodel biomembranesSTEDtunable surface chargecell membranesNanoscale Heterogeneities Drive Enhanced Binding
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