bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2021,
Номер
unknown
Опубликована: Апрель 27, 2021
Abstract
Cell
mechanical
properties
determine
many
physiological
functions,
such
as
cell
fate
specification,
migration,
or
circulation
through
vasculature.
Identifying
factors
that
govern
the
is
therefore
a
subject
of
great
interest.
Here
we
present
mechanomics
approach
for
establishing
links
between
single-cell
phenotype
changes
and
genes
involved
in
driving
them.
We
combine
characterization
cells
across
variety
mouse
human
systems
with
machine
learning-based
discriminative
network
analysis
associated
transcriptomic
profiles
to
infer
conserved
module
five
putative
roles
mechanics
regulation.
validate
silico
identified
gene
markers
are
universal,
trustworthy
specific
studied
systems,
demonstrate
experimentally
selected
target,
CAV1
,
accordingly
when
silenced
overexpressed.
Our
data-driven
paves
way
towards
engineering
on
demand
explore
their
impact
pathological
functions.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(6), С. 2767 - 2767
Опубликована: Март 19, 2025
Glioblastoma
multiforme
(grade
IV
glioma)
is
characterized
by
a
high
invasive
potential,
making
surgical
intervention
extremely
challenging
and
patient
survival
very
limited.
Current
pharmacological
approaches
show,
at
best,
slight
improvements
in
the
therapy
against
this
type
of
tumor.
Microtubules
are
often
target
antitumoral
drugs,
specific
drugs
affecting
their
dynamics
acting
on
microtubule-associated
proteins
(MAPs)
without
producing
depolymerization
could
affect
both
glioma
cell
migration/invasion
proliferation.
Here,
we
analyzed
cellular
model
glioblastoma
multiforme,
effect
molecule
(1-(4-amino-3,5-dimethylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4h2,3-benzodiazepin-4-one,
hereafter
named
1g)
which
was
shown
to
act
as
cytostatic
drug
other
types
microtubule
dynamics.
We
found
that
acts
also
migration
suppressor
inducing
loss
polarity.
mechanics
U87MG
aggregates
exposed
1g
different
biophysical
techniques.
considered
3D
2D
cultures,
testing
substrates
stiffness.
established
produces
decrease
spheroid
contractility
it
impairs
invasion.
At
same
time,
case
isolated
cells,
selectively
an
almost
instantaneous
polarity
blocking
disorganization
mitotic
spindle
when
cells
reach
mitosis,
leading
frequent
slippage
events
followed
death.
can
state
studied
similar
effects
molecules
known
microtubules,
but
probably
indirectly
via
following
biochemical
pathways.
Consistently,
report
evidence
that,
regarding
its
morphology,
shows
specificity
for
some
such
cells.
Interestingly,
being
derived
from
benzodiazepine,
chemical
structure
allow
easily
cross
blood–brain
barrier.
Thanks
chemical/physical
properties,
be
promising
new
treatment
GBM.
Cell
mechanical
properties
determine
many
physiological
functions,
such
as
cell
fate
specification,
migration,
or
circulation
through
vasculature.
Identifying
factors
that
govern
the
is
therefore
a
subject
of
great
interest.
Here,
we
present
mechanomics
approach
for
establishing
links
between
single-cell
phenotype
changes
and
genes
involved
in
driving
them.
We
combine
characterization
cells
across
variety
mouse
human
systems
with
machine
learning-based
discriminative
network
analysis
associated
transcriptomic
profiles
to
infer
conserved
module
five
putative
roles
mechanics
regulation.
validate
silico
identified
gene
markers
are
universal,
trustworthy,
specific
studied
systems,
demonstrate
experimentally
selected
target,
CAV1
,
accordingly
when
silenced
overexpressed.
Our
data-driven
paves
way
toward
engineering
on
demand
explore
their
impact
pathological
functions.
The
micromechanical
measurement
field
has
struggled
to
establish
repeatable
techniques
because
the
deforming
stresses
can
be
difficult
model.
A
recent
numerical
study
[Lu
et
al.,
J.
Fluid
Mech.
962,
A26
(2023)]
showed
that
viscoelastic
capsules
flowing
through
a
cross-slot
achieve
quasi-steady
strain
near
extensional
flow
stagnation
point
is
equal
equilibrium
static
strain,
thereby
implying
capsule's
elastic
behavior
captured
in
continuous
device
operation.
However,
no
experimental
microfluidic
studies
have
reported
strains
for
suspended
cells
or
particles
our
knowledge.
Here,
we
demonstrate
experimentally
conditions
necessary
replicate
uniaxial
creep
test
at
microscale
and
relatively
high
throughput.
By
using
large
dimension
cross-slots
relative
microparticle
diameter,
implementation
creates
an
region
enough
agarose
hydrogel
microparticles
plateau
while
dwelling
point.
This
will
key
accurately
precisely
measuring
properties
of
small
biological
objects.
We
propose
analytical
mechanical
model
extract
linear
from
observed
particle
histories.
Particle
image
velocimetry
measurements
unperturbed
velocity
used
estimate
where
experienced
might
applied
property
measurements.
Finally,
provide
recommendations
applying
experiment
other
biomaterials
criteria
identify
likely
achieved
state.
npj Biological Physics and Mechanics.,
Год журнала:
2025,
Номер
2(1)
Опубликована: Апрель 3, 2025
Abstract
For
several
decades,
research
has
studied
the
influence
of
extracellular
matrix
(ECM)
mechanical
properties
in
cell
response,
primarily
emphasising
its
elasticity
as
main
determinant
and
tissue
behaviour.
However,
ECM
is
not
purely
elastic;
it
viscoelastic.
viscoelasticity
now
emerged
a
major
regulator
collective
dynamics.
This
review
highlights
recent
findings
on
role
development
pathology.
