Spectrin mediates 3D-specific matrix stress-relaxation response in neural stem cell lineage commitment
Science Advances,
Год журнала:
2024,
Номер
10(31)
Опубликована: Авг. 2, 2024
While
extracellular
matrix
(ECM)
stress
relaxation
is
increasingly
appreciated
to
regulate
stem
cell
fate
commitment
and
other
behaviors,
much
remains
unknown
about
how
cells
process
stress-relaxation
cues
in
tissue-like
three-dimensional
(3D)
geometries
versus
traditional
2D
culture.
Here,
we
develop
an
oligonucleotide-crosslinked
hyaluronic
acid–based
ECM
platform
with
tunable
properties
capable
of
use
either
or
3D.
Strikingly,
favors
neural
(NSC)
neurogenesis
3D
but
suppresses
it
2D.
RNA
sequencing
functional
studies
implicate
the
membrane-associated
protein
spectrin
as
a
key
3D-specific
transducer
cues.
Confining
drives
spectrin’s
recruitment
F-actin
cytoskeleton,
where
mechanically
reinforces
cortex
potentiates
mechanotransductive
signaling.
Increased
expression
also
accompanied
by
increased
transcription
factor
EGR1,
which
previously
showed
mediates
NSC
stiffness-dependent
lineage
Our
work
highlights
important
molecular
sensor
Язык: Английский
Viscoelastic High‐Molecular‐Weight Hyaluronic Acid Hydrogels Support Rapid Glioblastoma Cell Invasion with Leader–Follower Dynamics
Advanced Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 7, 2024
Hyaluronic
acid
(HA),
the
primary
component
of
brain
extracellular
matrix,
is
increasingly
used
to
model
neuropathological
processes,
including
glioblastoma
(GBM)
tumor
invasion.
While
elastic
hydrogels
based
on
crosslinked
low-molecular-weight
(LMW)
HA
are
widely
exploited
for
this
purpose
and
have
proven
valuable
discovery
screening,
tissue
both
viscoelastic
rich
in
high-MW
(HMW)
HA,
it
remains
unclear
how
these
differences
influence
To
address
question,
comprised
either
HMW
(1.5
MDa)
or
LMW
(60
kDa)
introduced,
characterized,
applied
GBM
invasion
studies.
Unlike
hydrogels,
relax
stresses
quickly,
a
similar
extent
as
tissue,
greater
than
many
conventional
HA-based
scaffolds.
cells
implanted
within
invade
much
more
rapidly
their
counterparts
exhibit
distinct
leader-follower
dynamics.
Leader
adopt
dendritic
morphologies
invasive
observed
vivo.
Transcriptomic,
pharmacologic,
imaging
studies
suggest
that
leader
exploit
hyaluronidase,
an
enzyme
strongly
enriched
human
GBMs,
prime
path
followers.
This
study
offers
new
insight
into
properties
drive
argues
use
highly
stress-relaxing
materials
GBM.
Язык: Английский