Passive transport across the lipid bilayer · Membrane passive transport mechanisms....
Transcript of Passive transport across the lipid bilayer · Membrane passive transport mechanisms....
Passive transport across the lipid bilayer
Lungs
Diffusion of gasses
Rate factors: membrane, temperature, distance, & size
Transmembrane diffusion: passive & down a concentration gradient
Membrane permeability to nonelectrolytes Steps (any can be rate limiting)
1) enter the membrane (potential barrier) 2) diffusion through the bilayer core 3) exit the membrane (potential barrier)
Free energy profiles for selected solutes
in a DPPC bilayer at 323 oK.
Membrane passive transport mechanisms. (A) Solubility-diffusion model. (B) Transient pore model. (C) Head-group gated model. (D) Lipid flipping-carrier model. Circles represent lipid head groups and the gray area indicates the hydrophobic region occupied by lipid acyl chains. The black oval is the solute molecule.
membrane out in
Con
cent
ratio
n
x l
Cout
Cin Cm1
Cm2
xCDJx ∂
∂−=
Fick’s 1st law
lCCD
tm
sJ mmx
211 −−=
∂
∂=
Fick’slawforpassivetransportofneutralpar4clesthroughthemembrane:
Diffusion coefficient profiles for selected solutes in a DPPC bilayer at 323 oK.
in
m
out
m
CC
CCK 21 ==
membrane out in
Con
cent
ratio
n
x l
Cout
Cin Cm1
Cm2
K =Cm
Cw
= exp µwo −µm
o
RT"
#$
%
&'
Cm – concentration just inside the hydrophobic core of the bilayer, Cw – concentration in the aqueous solution.
The chemical potential in the water phase (µw) = the chemical potential in the membrane (µm):
mommw
oww CRTCRT lnln +==+= µµµµ
The concentration at the surface of the membrane (Cm) ⎟⎟
⎠
⎞⎜⎜⎝
⎛ −=
RTCC
om
ow
wmµµexp
The membrane:water partition coefficient (Kp)
membrane out in
Con
cent
ratio
n
x l
Cout
Cin Cm1
Cm2
Flux, and therefore the rate of transfer across the membrane are proportional to the partitioning coefficient.
Partitioning coefficient is a quantitative measure of the how lipophilic is the compound.
Higher partitioning coefficient indicates better solubility and faster transport across the membrane
Fick’s law for passive transport of neutral particles through the membrane:
( )oi
om
ow CCRTd
DJ −⎟⎟⎠
⎞⎜⎜⎝
⎛ −−=
µµexp
The permeability coefficient
⎟⎟⎠
⎞⎜⎜⎝
⎛ −⎟⎠
⎞⎜⎝
⎛=RTd
DPom
ow µµexp
dDKP P=
Permeability coefficients are a combined property of the solute
and the membrane system.
xCDJx ∂
∂−=
J = −DdK Ci −Co( )
P in membranes is strongly correlated with K for nonpolar solvent
Physicochemical and RBC
distributional properties for
water, urea and thiourea
Molecule diffusion across the aqueous layers
adjacent to either surface of the membrane.
Unstirred Layers
1 µm to 500 µm thickness.
For water soluble compounds – diffusion across the unstirred layers will have relatively less effect.
It is most prominent for relatively nonpolar compounds – the diffusion across the membrane itself will be relatively fast.
P – a membrane permeability coefficient
D – an aqueous diffusion constant.
di and do – the thicknesses of unstirred layers.
Ci and Co – the bulk concentrations of the compound,
Cmi and Cmo – the concentrations at the surface of the membrane.
§ The flow through the membrane is ( )momim CCPJ −=§ The flow through the unstirred layers
( )miii
i CCdDJ −=( )omo
oo CCdDJ −=
Therefore momi CCPJ
−= miii CCDJd
−= omoo CCDJd
−=
After summing: oioi CCDd
Dd
PJ −=⎟
⎠
⎞⎜⎝
⎛ ++1
The effect of unstirred layers is to decrease the permeability so the apparent permeability coefficient (Papp) is smaller than P:
Dd
Dd
PPoi
app
++=11
At steady-state JJJJ oim ===