bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 13, 2025
Abstract
Enhancing
protocols
and
methods
for
producing
therapeutic
extracellular
vesicles
(EVs)
in
bioreactors
is
crucial
to
achieve
scalable
production
while
ensuring
both
quality
quantity.
Studies
have
shown
that
mechanical
stress
can
promote
EV
release,
although
the
underlying
mechanisms
remain
largely
unclear.
Here
we
investigated
which
are
responsible
increase
of
under
shear
stress.
EVs
were
produced
from
adipose
tissue-derived
stromal
cells
(ASCs),
also
described
as
mesenchymal
(MSCs)
support
regeneration
injured
tissues
via
several
paracrine
factors.
The
cultures
treated
with
GsMTx4,
an
inhibitor
blocks
Piezo1
ion
channels,
or
YODA1,
its
agonist,
assess
if
forces
pathways
involved
enhancing
release.
quantified
characterized
after
high
(HS)
stimulation
compared
no
(3D)
standard
(2D).
These
experiments
showed
that,
by
stress,
increased
this
effect
was
blocked
inhibition
channels
GsMTx4
(88%)
impact
on
cell
viability.
Consistently,
agonist
YODA1
(149%).
implications
these
findings
significant,
especially
regenerative
medicine
cellular
therapies,
where
efficient
high-quality
crucial.
By
understanding
turbulence-induced
natural
mechanotransductive
within
cells,
it
may
be
possible
optimize
EVs,
paving
way
more
effective
treatments
future.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 26, 2024
Idiopathic
pulmonary
fibrosis
(IPF)
is
a
lung
disease
that
worsens
over
time,
causing
in
the
lungs
and
ultimately
resulting
respiratory
failure
high
risk
of
death.
Macrophages
play
crucial
role
immune
system,
showing
flexibility
by
transforming
into
either
pro-inflammatory
(M1)
or
anti-inflammatory
(M2)
macrophages
when
exposed
to
different
stimuli,
impacting
development
IPF.
Recent
research
has
indicated
polarization
onset
progression
M1
secrete
inflammatory
cytokines
agents
early
damage
fibrosis,
while
M2
support
tissue
healing
releasing
cytokines.
Developing
novel
treatments
for
IPF
relies
on
thorough
comprehension
processes
involved
macrophage
The
review
outlines
regulation
its
impact
IPF,
with
goal
investigating
possible
therapeutic
benefits
advancement
Biomolecules,
Год журнала:
2024,
Номер
14(9), С. 1186 - 1186
Опубликована: Сен. 20, 2024
Glycosaminoglycans
(GAGs)
and
proteoglycans
(PGs)
are
essential
components
of
the
extracellular
matrix
(ECM)
with
pivotal
roles
in
cellular
mechanosensing
pathways.
GAGs,
such
as
heparan
sulfate
(HS)
chondroitin
(CS),
interact
various
cell
surface
receptors,
including
integrins
receptor
tyrosine
kinases,
to
modulate
responses
mechanical
stimuli.
PGs,
comprising
a
core
protein
covalently
attached
GAG
chains,
serve
dynamic
regulators
tissue
mechanics
behavior,
thereby
playing
crucial
role
maintaining
homeostasis.
Dysregulation
GAG/PG-mediated
pathways
is
implicated
numerous
pathological
conditions,
cancer
inflammation.
Understanding
intricate
mechanisms
by
which
GAGs
PGs
forces
holds
promise
for
developing
novel
therapeutic
strategies
targeting
mechanotransduction
disease.
This
comprehensive
overview
underscores
importance
key
mediators
homeostasis
their
potential
targets
mitigating
mechano-driven
pathologies,
focusing
on
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(4), С. 2135 - 2135
Опубликована: Фев. 10, 2024
Contact
inhibition
(CI)
represents
a
crucial
tumor-suppressive
mechanism
responsible
for
controlling
the
unbridled
growth
of
cells,
thus
preventing
formation
cancerous
tissues.
CI
can
be
further
categorized
into
two
distinct
yet
interrelated
components:
locomotion
(CIL)
and
proliferation
(CIP).
These
components
have
historically
been
viewed
as
separate
processes,
but
emerging
research
suggests
that
they
may
regulated
by
both
shared
pathways.
Specifically,
recent
studies
indicated
CIP
CIL
utilize
mechanotransduction
pathways,
process
involves
cells
sensing
responding
to
mechanical
forces.
This
review
article
describes
role
in
CI,
shedding
light
on
how
forces
regulate
CIP.
Emphasis
is
placed
filamin
A
(FLNA)-mediated
mechanotransduction,
elucidating
FLNA
senses
translates
them
biochemical
signals
cell
proliferation.
In
addition
FLNA,
trans-acting
factors
(TAFs),
which
are
proteins
or
regulatory
RNAs
capable
directly
indirectly
binding
specific
DNA
sequences
distant
genes
gene
expression,
emerge
sensitive
players
signaling
pathways
CI.
presents
methods
identifying
these
TAF
profiling
associated
changes
chromatin
structure,
offering
valuable
insights
other
biological
functions
mediated
mechanotransduction.
Finally,
it
addresses
unanswered
questions
fields
delineates
their
possible
future
directions.
Abstract
Integrins
are
critical
transmembrane
receptors
that
connect
the
extracellular
matrix
(ECM)
to
intracellular
cytoskeleton,
playing
a
central
role
in
mechanotransduction
–
process
by
which
cells
convert
mechanical
stimuli
into
biochemical
signals.
The
dynamic
assembly
and
disassembly
of
integrin-mediated
adhesions
enable
adapt
continuously
changing
cues,
regulating
essential
processes
such
as
adhesion,
migration,
proliferation.
In
this
review,
we
explore
molecular
clutch
model
framework
for
understanding
dynamics
integrin
ECM
interactions,
emphasizing
importance
force
loading
rate.
We
discuss
how
rate
bridges
internal
actomyosin-generated
forces
properties
like
stiffness
ligand
density,
determining
whether
sufficient
is
transmitted
mechanosensitive
proteins
talin.
This
transmission
leads
talin
unfolding
activation
downstream
signalling
pathways,
ultimately
influencing
cellular
responses.
also
examine
recent
advances
single-molecule
DNA
tension
sensors
have
enabled
direct
measurements
rates,
refining
range
approximately
0.5–4
pN/s.
These
findings
deepen
our
force-mediated
underscore
need
improved
sensor
designs
overcome
current
limitations.
Biomarker Research,
Год журнала:
2025,
Номер
13(1)
Опубликована: Янв. 23, 2025
The
tumor
microenvironment
functions
as
a
dynamic
and
intricate
ecosystem,
comprising
diverse
array
of
cellular
non-cellular
components
that
precisely
orchestrate
pivotal
behaviors,
including
invasion,
metastasis,
drug
resistance.
While
unraveling
the
interplay
between
behaviors
represents
tremendous
challenge,
recent
research
illuminates
crucial
biological
phenomenon
known
mechanotransduction.
Within
microenvironment,
mechanical
cues
like
tensile
stress,
shear
stiffness
play
role
by
activating
mechanosensitive
effectors
such
PIEZO
proteins,
integrins,
Yes-associated
protein.
This
activation
initiates
cascades
intrinsic
signaling
pathways,
effectively
linking
physical
properties
tissues
to
their
physiological
pathophysiological
processes
morphogenesis,
regeneration,
immunity.
mechanistic
insight
offers
novel
perspective
on
how
within
impact
behaviors.
intricacies
are
yet
be
fully
elucidated,
it
exhibits
distinct
attributes
from
non-malignant
tissues,
elevated
solid
stresses,
interstitial
hypertension,
augmented
matrix
stiffness,
enhanced
viscoelasticity.
These
traits
exert
notable
influences
progression
treatment
responses,
enriching
our
comprehension
multifaceted
nature
microenvironment.
Through
this
innovative
review,
we
aim
provide
new
lens
decipher
contexts,
broadening
knowledge
these
factors
promote
or
inhibit
thus
offering
valuable
insights
identify
potential
targets
for
anti-tumor
strategies.
DNA
nanotechnology
represents
an
innovative
discipline
that
combines
with
biotechnology.
It
exploits
the
distinctive
characteristics
of
deoxyribonucleic
acid
(DNA)
to
create
nanoscale
structures
and
devices
remarkable
accuracy
functionality.
Researchers
may
complex
nanostructures
precision
specialized
functions
using
DNA's
innate
stability,
adaptability,
capacity
self-assemble
through
complementary
base-pairing
interactions.
Integrating
multiple
disciplines,
known
as
nanobiotechnology,
allows
production
sophisticated
nanodevices
a
broad
range
applications.
These
include
precise
drug
delivery
systems,
extremely
sensitive
biosensors,
construction
intricate
tissue
scaffolds
for
regenerative
medicine.
Moreover,
combining
mechanobiology
provides
new
understanding
how
small-scale
mechanical
stresses
molecular
interactions
affect
cellular
activity
development.
has
potential
revolutionize
diagnostics,
engineering,
organ
regeneration.
This
could
lead
enormous
improvements
in
biomedicine.
review
emphasizes
most
recent
developments
nanotechnology,
explicitly
highlighting
its
significant
influence
on
growing
involvement
engineering.
extensive
overview
present
trends,
obstacles,
future
prospects
this
fast-progressing
area.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2023,
Номер
42(1)
Опубликована: Дек. 20, 2023
Abstract
In
recent
years,
research
focused
on
the
multifaceted
landscape
and
functions
of
cancer-associated
fibroblasts
(CAFs)
aimed
to
reveal
their
heterogeneity
identify
commonalities
across
diverse
tumors
for
more
effective
therapeutic
targeting
pro-tumoral
stromal
microenvironment.
However,
a
unified
functional
categorization
CAF
subsets
remains
elusive,
posing
challenges
development
targeted
therapies
in
clinical
settings.
The
phenotype
arises
from
complex
interplay
signals
within
tumor
microenvironment,
where
transcription
factors
serve
as
central
mediators
various
cellular
pathways.
Recent
advances
single-cell
RNA
sequencing
technology
have
emphasized
role
conversion
normal
distinct
subtypes
cancer
types.
This
review
provides
comprehensive
overview
specific
roles
factor
networks
shaping
heterogeneity,
plasticity,
functionality.
Beginning
with
influence
fibroblast
homeostasis
reprogramming
during
wound
healing
fibrosis,
it
delves
into
emerging
insights
regulatory
networks.
Understanding
these
mechanisms
not
only
enables
precise
characterization
but
also
sheds
light
early
processes
governing
Ultimately,
this
knowledge
may
unveil
novel
targets
treatment,
addressing
existing
stromal-targeted
therapies.
