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E-‐cadherin
adhesions
play
important
roles
in
the
development
and
maintenance
of
tissue
structure
in
multi-‐cellular
organisms,
thus
serving
as
a
key
element
of
the
cellular
microenvironment
providing
both
mechanical
and
biochemical
signaling
inputs.
This
requires
interaction
between
extracellular
domains
of
E-‐
cadherin
(E-‐cad-‐ECD)
from
apposing
cells,
as
well
as
the
interaction
of
the
intracellular
domain
of
E-‐cadherin
(E-‐cad-‐ICD)
with
the
actin
cytoskeleton.
The
later
is
mediated
by
α-‐catenin,
which
is
postulated
to
undergo
a
force-‐
dependent,
reversible
conformational
change.
We
use
hybrid
adhesions
formed
between
a
live
cell
and
a
synthetic,
E-‐cad-‐ECD-‐functionalized
supported
lipid
bilayer
to
understand
the
process
of
adhesion
formation
and
the
regulation
of
α-‐
catenin
conformation
therein.
Cells
interacted
with
E-‐cad-‐ECD
bilayers
by
extending
filopodia,
and
retraction
of
which
resulted
in
E-‐cadherin
clustering
and
subsequent
fusion
of
these
clusters
to
give
rise
to
large-‐scale
molecular
assemblies.
Adhesion
formation
required
both
active
processes
within
the
living
cell
and
a
supported
lipid
bilayer
with
low
E-‐cad-‐ECD
mobility,
suggesting
a
nucleation
step
in
E-‐cadherin
clustering.
Further,
large-‐scale
assemblies
of
E-‐
cadherin
clusters
contained
α-‐catenin
in
the
‘open’
conformation,
irrespective
of
their
association
with
the
actin
cytoskeleton.
Abrogation
of
the
assembly
process
using
micropatterned
substrates,
however,
resulted
in
a
decrease
in
the
levels
of
structurally
‘open’
α-‐catenin.
Therefore,
E-‐cadherin
adhesion
formation
is
an
active
process
involving
a
nucleation
step,
and
the
large-‐scale
assembly
of
E-‐
cadherin
clusters
controls
mechanotransduction
by
influencing
the
conformation
of
α-‐catenin. |