MICROVASCULAR RESEARCH 20,96-E (1980)

A Fiber Matrix Model of Capillary Permeability

F. E. CURRY

Department of Human Physiology, University of California at Davis, Davis, California 95616

AND

C. C. MICHEL
University Laboratory of Physiology, Oxford, OX1 3PT, United Kingdom

Received October 31, 1979

The observation that ferritin is excluded from the luminal vesicles and the
luminal surface of endothelial cells has led one of us (Michel, 1978a, 1979) to
reintroduce the idea that the molecular sieving properties of the capillary wall may
reside in an endocapillary layer rather than in the dimensions of pores through or
between the endothelial cells. It is suggested that the endocapillary layer is a
three-dimensional network formed by the fibrous chains of the membrane glyco-
proteins of the endothelial cell coat reinforced by the absorption of plasma proteins
(Mason et al., 1977). It may be identified with the ruthenium red staining layer
described by Luft (1966). The latter not only appears to line the luminal surface of
the capillary but also appears to fill the wide regions of the intercellular clefts and
merge with the basal lamina. It is found covering the fenestrations when these are
present and can also be seen lining the cytoplasmic vesicles (Shirahama and
Cohen, 1972).
In this short paper, we wish to draw attention to the possible relationships for
flow and diffusion through such a membrane, and so offer a quantitative basis for
assessing the theory.

THEORY
The porous regions of the capillary wall are considered as a series of channels
through or between the endothelial cells containing a random array of cylindrical
fibers. The radius of the fibers, rr, is constant and their concentration in the porous
region can be expressed as 1, the length of fiber per unit volume. Thus only a
fraction, E, of the volume of the porous region will be occupied by aqueous
solution, the remainder of the volume being filled by the fibers and having a value
of mf21 (i.e., 1 - E = ~121). The area of the porous regions per unit area of capillary
wall, A,, is a very small fraction and the average length of the porous channels,
Ax, may exceed the average wall thickness.
The flow of a fluid through a random arrangement of fibers has been considered
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at a macroscopic level and has been found to be described by the Carman-Kozeny

equation (see Sullivan and Hertel, 1942, and Happel and Brenner, 1965, for
review). This may be written as:
A, rf . - 63
J, = hp . -. -
(l-e)2 ’
(1)
Ax 4K7)
where J, = volume flow per unit area of membrane; AP = pressure drop across
membrane; q = viscosity of the fluid; and K = Kozeny constant.
The Kozeny constant is dependent on the geometry of the channels in the
porous medium. For a random array of fibers it is fairly constant (ca.5.0) with
values of E less than 0.90. In macroscopic systems K appears to rise rapidly as E
approaches 1.Obut at a molecular level Ogston and Woods (1954) found that when
Eq. (1) was used to describe the sedimentation of dextrans, K remained constant
for values of E up to 0.98.
An expression which successfully describes the diffusion of a molecule through
a random array of fibers of molecular dimensions has been described by Ogston et
al. (1973). Using a stochastic model for diffusion, they predicted that the diffusion
coefficient, D, of a spherical molecule within a fibrous network should be related
to its value in aqueous solution, D,, through the expression:
D = D, exp {- 7ro.5P.5 (a + rJ}, (2)
where a is the radius of the spherical molecule. Equation (2) also describes the
solute diffusion coefficient in a fibrous membrane. A membrane partition
coefficient, 4, may be calculated from Ogston’s (1958) theory of the distribution of
spaces within a random array of fibers:
C#J
= exp {- nl(2arr + a”)}. (3)
Thus the permeability of the fibrous membrane, P,, should be described by:

P,= $.D,exp{- 7i-o.5IO.5(a + Yf) - Tf(2uarf + u”)}.

Anderson and Malone (1974) have described a relation between the osmotic
reflection coefficient of a membrane and the steric forces acting on a spherical
solute within cylindrical water filled channels through the membrane:
u = (1 - 4)‘. (5)
Recent theoretical and experimental studies (Anderson, personal communication)
indicate that Eq. (5) appears to describe u for membranes penetrated by aqueous
channels having a variety of geometries.
If Eq. (5) does possess the generality which Anderson’s findings suggest, Eqs.
(l), (4), and (5) provide a quantitative description for hydrostatic and osmotic flow
and for diffusion through a fiber matrix membrane.

DISCUSSION
If Eqs. (I), (4), and (5) are now used to analyze recent measurements of
capillary permeability made on single vessels in the frog mesentery, they reveal an
98 BRIEF COMMUNICATIONS

internal consistency which the pore theory of capillary permeability fails to offer.
Calculations based on the pore theory and fiber matrix theory examining the same
permeability data are summarized below. Measurements of the osmotic reflection
coefficients of capillary walls to small molecules suggested that the pore radii lay
in the region of 5.0 to 10.0 nm (Curry et al., 1976). More recent measurements of
permeability coefficients to K+ (Crone et al., 1978) and to small hydrophilic
molecules (Curry, 1979) when combined with filtration coefficients (L,) for the
same capillaries yield values for pore radius of 10 nm or more. These pore radii
seem inconsistent with measurements of (+ for myoglobin and serum albumin
(Michel, 1977) which suggest values for pore radius of 5-6 nm. It seems unlikely
that this discrepancy in the calculation of pore radius can be accounted for entirely
in terms of the charge on the macromolecules, for the isoelectric point for serum
albumin is 5.16 whereas that for myoglobin is 7.8.
When these data are examined from the point of view of the fiber matrix theory,
a single value of E is found consistent with all permeability values. Taking the
value for rr of a sialoglycoprotein, 0.6 nm (Latta et al., 1975), Eq. (5) predicts that
when E = 0.95, (T for myoglobin = 0.31 and o for serum albumin = 0.82. These
values are close to those determined by Michel. Following Crone et al. and taking
a value of L, of 5.4 x 10e3pm set-l cm H,O-‘, AJAX can be calculated from Eq.
(1) (using K = 5) with rf = 0.6 nm and E = 0.95 and is found to be 80.3 cm-‘. Thus
the permeability to a small potassium ion (a - 0.2 nm) should be around 105 x 10e5
cm see-’ which is within the range of values measured by Crone et al. The same
values of rf and E are consistent with Curry’s measurements of the permeability of
sodium chloride and sucrose in capillaries of known L,.
We have also investigated other combinations of rf and E. The internal consis-
tency described above is not found for values of rf larger than 1 nm. On the other
hand, preliminary applications of the model to investigate the changes in the
conductivity of the capillary wall when proteins are removed from the perfusate
(Mason et al., 1977) suggest there is an increase in E (decreased fiber volume) at
constant rf. (See Curry, 1980, for further evaluation of the model.)
There is another attractive feature of the fiber matrix theory of capillary per-
meability. When permeability measurements are made on single capillaries, there
is considerable variation from one vessel to another even though the vessels
appear to be undamaged. While permeability and filtration coefficients vary, the
porosity of the capillary wall assessed either as the ratio of permeability to
filtration coefficient (Curry, 1979) or as the reflection coefficient to mac-
romolecules (Michel, 1978b) appears to be constant. This implies that whereas
the number of transcapillary channels varies from one site to another in the
capillary bed, the frictional resistance of the channels remains constant. Accord-
ing to the fiber matrix theory, the molecular sieving properties of the capillary wall
are determined by the fiber matrix. The variations in permeability between differ-
ent capillaries could be determined by variations in the number of channels
through the endothelium and yet, if all the channels were covered (or filled) with
fibers at the same concentration, the molecular selectivity of the capillary wall
would remain constant.
Of further interest in this respect is the remarkable similarity of protein permea-
bility and reflection coefficient in fenestrated and in continuous capillaries in spite
of their differences in filtration coefficient and ultrastructure (Renkin, 1977).
 BRIEF COMMUNICATIONS 99

ACKNOWLEDGMENT
Supported, in part, by NIH Research Grant HL 18010.

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