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@ARTICLE{GaikoShcherbak:280377,
author = {Gaiko-Shcherbak, Aljona and Fabris, Gloria and Dreissen,
Georg and Merkel, Rudolf and Hoffmann, Bernd and Noetzel,
Erik},
title = {{T}he {A}cinar {C}age: {B}asement {M}embranes {D}etermine
{M}olecule {E}xchange and {M}echanical {S}tability of
{H}uman {B}reast {C}ell {A}cini},
journal = {PLoS one},
volume = {10},
number = {12},
issn = {1932-6203},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {FZJ-2016-00154},
pages = {e0145174 -},
year = {2015},
abstract = {The biophysical properties of the basement membrane that
surrounds human breast glands are poorly understood, but are
thought to be decisive for normal organ function and
malignancy. Here, we characterize the breast gland basement
membrane with a focus on molecule permeation and mechanical
stability, both crucial for organ function. We used
well-established and nature-mimicking MCF10A acini as 3D
cell model for human breast glands, with ether low- or
highly-developed basement membrane scaffolds.
Semi-quantitative dextran tracer (3 to 40 kDa) experiments
allowed us to investigate the basement membrane scaffold as
a molecule diffusion barrier in human breast acini in vitro.
We demonstrated that molecule permeation correlated
positively with macromolecule size and intriguingly also
with basement membrane development state, revealing a pore
size of at least 9 nm. Notably, an intact collagen IV mesh
proved to be essential for this permeation function.
Furthermore, we performed ultra-sensitive atomic force
microscopy to quantify the response of native breast acini
and of decellularized basement membrane shells against
mechanical indentation. We found a clear correlation between
increasing acinar force resistance and basement membrane
formation stage. Most important native acini with
highly-developed basement membranes as well as cell-free
basement membrane shells could both withstand
physiologically relevant loads (≤ 20 nN) without loss of
structural integrity. In contrast, low-developed basement
membranes were significantly softer and more fragile. In
conclusion, our study emphasizes the key role of the
basement membrane as conductor of acinar molecule influx and
mechanical stability of human breast glands, which are
fundamental for normal organ function.},
cin = {ICS-7},
ddc = {500},
cid = {I:(DE-Juel1)ICS-7-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000366722700110},
doi = {10.1371/journal.pone.0145174},
url = {https://juser.fz-juelich.de/record/280377},
}