Biomedical Engineering Reference
In-Depth Information
Nanoscale mucus rheology assessed by amplitude and time scale of
geometrically averaged ensemble mean-square displacements of fluorescent
particles
23
can change without influencing macrorheological properties measured
by torque required to apply a small-amplitude oscillatory stress at specified
frequencies using a cone-and-plate rheometer [
1566
]. Brownian displacements
of non-interacting beads (coated with a non-mucoadhesive surface) is more or less
precluded according to bead size. Rheological parameters vary according to trapped
particle size.
24
Many factors contribute to mucus rheology, such as mucus glycoprotein type,
hydration degree, and crosslink density [
1567
]. The latter is influenced by pH
and ion content as well as the presence of possible inflammatory mediators and
enzymes. Mucolytics reduce viscosity by disrupting polymer network in airway
surface liquid. Classical mucolytics work by severing of disulfide bonds, binding
of calcium, depolymerizing mucopolysaccharides and liquefying proteins. Some
peptide mucolytics degrade DNA and actin.
Microrheology of human mucus deals with behavior at length scale of pores
in mucus mesh and macromolecules (
[10-100 nm]).
Microviscosity at length scales higher than average interfiber spacing is associated
with a transport rate that can be assessed by particle tracking. Diffusion at these
length scales in mucus appears to be similar as that in water [
1566
]. Nanopolymers
with a characteristic length of few to several hundreds of nanometers are able to
cross mucus with only 4- to 6-fold decrease in effective diffusivity with respect
to water. Conversely, heterogeneity of mucus mesh that results from increased
content in nanoparticles entrapped in mucus could create larger pores for mass
transfer [
1566
]
O
[1 nm]) or nanoparticles (
O
23
The bulk elastic modulus of concentrated isotropic solutions of entangled polymers is described
by the storage modulus. The storage modulus for semiflexible, flexible, and stiff, crosslinked
polymer networks is estimated by [
1566
]:
G
(
ω
)
∼
κ
2
ξ
−
2
L
−
3
c
/
k
B
T
(
xi
: mesh size;
L
c
chain length;
k
B
T
: thermal energy;
k
B
:Boltzmann constant;
T
: absolute temper-
ature; and
k
B
T
),
G
(
ω
)
∼
κ
2
ξ
−
5
κ
is related to the persistence length of the chain
Lp
≈
κ
/
/
k
B
T
,
and
G
(
ω
)
∼
ξ
−
3
k
B
T
, respectively. The viscoelastic spectrum
G
r
2
(
s
)=
2
k
B
T
/
3
π
Rs
<
Δ
(
s
)
>
r
2
(
R
: particle radius;
s
: Laplace frequency; and
<
Δ
(
s
)
>
: unilateral Laplace transform of time-
r
2
2
2
(
x
averaged, mean-square displacement
Δ
(
τ
))
>
=
<
[
x
(
t
+
τ
)
−
x
(
t
)]
+[
y
(
t
+
τ
)
−
y
(
t
)]
(
t
)
,
y
(
t
)
:
nanoparticle coordinates at a given time
t
;and
τ
time scale). The Fourier transform equivalent of
is the complex shear modulus
G
∗
(
ω
)
G
[
1566
]. The complex shear modulus of mucus that bears
oscillatory deformations of small amplitude (1% strain) yields frequency-dependent (dynamic),
storage (elastic;
G
(
ω
)
(
s
)
), and loss (viscous;
G
(
ω
)
) moduli, which are in-phase and out-of-phase
components with respect to loading, respectively.
24
Effective storage modulus of cervicovaginal mucus at the lowest loading frequency is equal to 1.0
and 4.3 mPa when mucus traps non-interacting 200- and 500-nm beads and 400 to 154,000 mPa
with 1-mm beads [
1566
]. In addition, loss modulus is higher than storage modulus for mucus
that traps 100- to 500-nm particles, and conversely for 1-mm beads. At high frequency, beads
sufficiently small relative to mesh spacing experience the viscous drag of interstitial fluid, whereas
at low frequency (large time scale), elastic behavior contributes to mucin mesh hindrance.
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