2 research outputs found
Peptides at the Interface: Self-Assembly of Amphiphilic Designer Peptides and Their Membrane Interaction Propensity
Self-assembling
amphiphilic designer peptides have been successfully
applied as nanomaterials in biomedical applications. Understanding
molecular interactions at the peptide–membrane interface is
crucial, since interactions at this site often determine (in)Âcompatibility.
The present study aims to elucidate how model membrane systems of
different complexity (in particular single-component phospholipid
bilayers and lipoproteins) respond to the presence of amphiphilic
designer peptides. We focused on two short anionic peptides, V<sub>4</sub>WD<sub>2</sub> and A<sub>6</sub>YD, which are structurally
similar but showed a different self-assembly behavior. A<sub>6</sub>YD self-assembled into high aspect ratio nanofibers at low peptide
concentrations, as evidenced by synchrotron small-angle X-ray scattering
and electron microscopy. These supramolecular assemblies coexisted
with membranes without remarkable interference. In contrast, V<sub>4</sub>WD<sub>2</sub> formed only loosely associated assemblies over
a large concentration regime, and the peptide promoted concentration-dependent
disorder on the membrane arrangement. Perturbation effects were observed
on both membrane systems although most likely induced by different
modes of action. These results suggest that membrane activity critically
depends on the peptide’s inherent ability to form highly cohesive
supramolecular structures
Development of an Advanced Intestinal in Vitro Triple Culture Permeability Model To Study Transport of Nanoparticles
Intestinal
epithelial cell culture models, such as Caco-2 cells,
are commonly used to assess absorption of drug molecules and transcytosis
of nanoparticles across the intestinal mucosa. However, it is known
that mucus strongly impacts nanoparticle mobility and that specialized
M cells are involved in particulate uptake. Thus, to get a clear understanding
of how nanoparticles interact with the intestinal mucosa, in vitro
models are necessary that integrate the main cell types. This work
aimed at developing an alternative in vitro permeability model based
on a triple culture: Caco-2 cells, mucus-secreting goblet cells and
M cells. Therefore, Caco-2 cells and mucus-secreting goblet cells
were cocultured on Transwells and Raji B cells were added to stimulate
differentiation of M cells. The in vitro triple culture model was
characterized regarding confluence, integrity, differentiation/expression
of M cells and cell surface architecture. Permeability of model drugs
and of 50 and 200 nm polystyrene nanoparticles was studied. Data from
the in vitro model were compared with ex vivo permeability results
(Ussing chambers and porcine intestine) and correlated well. Nanoparticle
uptake was size-dependent and strongly impacted by the mucus layer.
Moreover, nanoparticle permeability studies clearly demonstrated that
particles were capable of penetrating the intestinal barrier mainly
via specialized M cells. It can be concluded that goblet cells and
M cells strongly impact nanoparticle uptake in the intestine and should
thus be integrated in an in vitro permeability model. The presented
model will be an efficient tool to study intestinal transcellular
uptake of particulate systems