BULLETIN OF

MATHEMATICAL BIOPHYSICS
VOLUME 1, NUMBER 4
DECEMSEa, 1939

A C O M P A R I S O N OF E L E C T R I C A L A N D D I F F U S I O N F O R C E S
IN T H E M E T A B O L I S M OF E L E C T R O L Y T E S

ROBERT R. W I L L I A M S O N
The U n i v e r s i t y of C h i c a g o

U s i n g a n a p p r o x i m a t i o n m e t h o d t h e electrical forces due to t h e

m e t a b o l i s m o f e l e c t r o l y t e s h a v e b e e n c o m p a r e d to t h e o r d i n a r y dif-
f u s i o n forces a n d f o u n d negligible.

In the development of mathematical biophysics it has been

assumed f o r the purposes of simplification t h a t electrical forces, cre-
ated b y a difference in the diffusion rates of positive and negative ions
produced or consumed in metabolic reaction, would have a negligible
effect on the concentration gradients of those ions. P r e l i m i n a r y con-
siderations led N. Rashevsky to believe this to be true. By w a y of a
preliminary s t u d y he considered the case of a spherical cell in which
the diffusion coefficients are infinite, and only the permeabilities finite
(Rashevsky, 1938, p. 126, h e r e i n a f t e r referred to as M.B.). In an
earlier paper (Rashevsky, 1.935) he discussed the equations for the
case of the consumption of two monovalent ions o f opposite charge,
present in equal quantities at an infinite distance f r o m the cell in
which they are consumed. Because of the difficulties in solving these
equations the problem has awaited quantitative t r e a t m e n t b y a n e w
approximation method (M.B. Appendix).
In this paper we shall apply an approximation method to the
case of a spherical cell metabolizing to produce monovalent ions of
opposite charge, which ions have different molecular weights and in-
ternal diffusion coefficients b u t infinite permeabilities. L a t e r we shall
consider the cases where the permeabilities and external diffusion
coefficients are finite and the cell is non-spherical.
In reasonably dilute solutionsl where no forces other t h a n those
produced by random molecular collisions are considered, Fick's law
m a y be held to apply to the diffusion of metabolites. When, however,
a field of force acting on the particles is present we m u s t use a more
general formulation of the diffusion problem.
--151--
152 M A T H E M A T I C A L BIOPHYSICS

Let
D = diffusion coefficient o f a n ion in c m ~ sec -~,
c = c o n c e n t r a t i o n o f a n ion in g m c m -~,
B = m o b i l i t y o f a n ion in sec g m -~,
f = f o r c e on a n ion in d y n e s ,
k ---- B o l t z m a n n c o n s t a n t = 1 9 4 • 10 -16 erg. d e g r e e -1,
T = absolute temperature,
J = r a t e o f t r a n s p o r t o f a n ion t h r o u g h t h e m e m b r a n e
in g m am -~ sec -~,
q = r a t e o f p r o d u c t i o n o f a n ion in g m c m -~ sec -1,
M ---- m o l e c u l a r w e i g h t o f a n ion,
N -- A v o g a d r o ' s n u m b e r ,
s = c h a r g e o n a n e l e c t r o n in E . S . U ,
E ---- n e t c h a r g e on t h e cell in E . S . U ,
K ---- dielectric c o n s t a n t of t h e i n t e r n a l m e d i u m ,
V -- v o l u m e o f t h e cell in c m 3,
ro ---- r a d i u s o f t h e cell in cm,

a n d let t h e s u b s c r i p t s H- a n d - - d e n o t e t h e ions to w h i c h t h e c o n s t 3 n t
applies. L e t a b a r i n d i c a t e " a v e r a g e , " a n d t h e s u b s c r i p t 0 " e x t e r n a l "
when applied to c.
Then we m a y write immediately the following relations:
D
B -- ; (1)
kT
J -- - - D g r a d c OFBfc ; (2)

q§ _ q- Co§ Co-
M. M_ ' M§ M_ ; L------f-- (3)
I f we c o n s i d e r t h a t c = f a p p r o x i m a t e l y a t ~ o / 2 , t h e n a p p r o x i m a t e l y
C-- Co
---D g r a d c = -[- 2D - - (4)
7"o

T h e t o t a l c h a r g e s o f t h e p o s i t i v e a n d n e g a t i v e ions c o n s i d e r e d sepa-
rately are
~§ ~_
~-§ e V a n d ~-_N s V ,

so t h a t w e m a y w r i t e t h e n e t c h a r g e on t h e cell as

~§ ~_
E--4nro~(~§ M_) N s . (5)

T h e f o r c e on a p o s i t i v e ion a t ro is
 ROBERT R. WILLIAMSON 153

Ee 4nroNe ~ .c, c_
(6)
f+--gr7 - 3K (M+ ~)"

T h e n f r o m equations ( 2) , ( 4) , and ( 6),

J+ = 2D+ -
C +- • CO+ _~ 4nr~ c+ c_ ~+;
To 3K M+ M_)
(7)
c-~Co- 4nroNe 2B_ c§ c_
J_ = 2D_
ro 3K (M+ M_ ) c ' "

T h e total t r a n s p o r t s and productions are

4 n r o 2J+, 4 n r o 2J_ and 4 / 3 n r o 3q+, 4 / 3 n r o 3q_. (8)

F r o m considerations of a m a t e r i a l balance in the s t a t i o n a r y state, and
f r o m equations (7) and (8) w e have, a f t e r r e a r r a n g i n g

N g- D+ - N ~: D+ - -
4 n ro2 K k T M+ c J - - 4 ~ ro ~K- -k T M_ C+ C-

-~- 6D+ c+ ~ ro2 q+ - - 6D+ Co+ ---- 0 ;

N e 2 D:- N e ~ D=- -
C, ~ ~ 4 r 'to ~ ~ C+ C -
4 n to ~ K k T M_ K k T M+

6D_ c_ - - r J q_ - - 6D_ Co_ ----0 .

Y g2
L e t 4 nro 2 K k T -- p and, a s s u m i n g K ---- 80 and ro ---- 10 -3 cm., we h a v e

p ---- 4.735 9 1012 . T h e n dividing the first of these equations by c. p

D+/M_ and the second by c_ p D _ / M § gives

- M_ - 6M_ 6M_ q+ r o *
c_=--c++-- --( +c+)" (a)
(9)
- M+ - 6M+ 6M+ . q_ ro2
C+ : - - C_-Jf - - - (b)
M_ e e C- ( -6D-
}-c~

I n t r o d u c i n g (9a) into (9b) and solving f o r ~+ we obtain a f t e r r e a r -

ranging
154 MATHEMATICAL BIOPHYSICS

_ ( 6M+ (q+ ro 2 ) / 6 D + --[- Co+

0 = cJ "-~ [ p 2
M+ (q_ro 2 , Co_)]~+2
2M_ "-6-D-/_t
(to)
9M- ( q+ ro 2 ~_
p " - 6 - 5 ? + - Co+) c+

~- 3M+ (q+ ro 2 .
-7" # "

Since the linear and constant terms in ~+ contain the factor 10 -~ but
in all other respects are similar to the square t e r m coefficient, t h e y
will be negligible with respect to it. Then we have, a f t e r dropping
them,

c+ -- M+ ( q_ r J ~- 1 . q+ r J 6M+
2M_ " 6D_ - - Co-) -~ ~ [-6-~+ -~- co+) P
or since
1 (q+ ro ~ .
-+- Co+) - M+
- (qfrJ~_co_)~ > > 6M+
2M_ b~_ p
we have
- q - ro 2 q§ re 2 . rio. . Co-

c+ -- M+ ( 12M_-------D- ~- 12M+D+ ~- ~ -t- - a ~ ) 9

By means of equation (3) this m a y be w r i t t e n as

c-+ = M+ (D+-{- D_ q+ ro 2 co+

D+D_ 12M~ -~-M-~+)
or simply
- q+ ro 2 D + - [ - D _
C+ - -
12 D+D_ ~ Co+ ; (11)
and similarly for c_
- q_ r J D+-[-D_
c_-- 1----~ D § -I-c~ (12)

Here we m a y note t h e similarity of s equations to those of the dif-

fusion of one substance as derived by the approximation method
(M. ]3. Appendix). When D+ > > D_, c§ is proportional to c_ and to
I / D , , and w h e n D _ > > D+, c-+ is proportional to c_ and to 1/D+.
When (11) and (12) a r e introduced into (5) we get
 ROBERT R. WILLIAMSON 155

4_nro3[D~_2r-_D-" q + . r o 2 D++D_rJ q
3 [ D+D_ M+ 12 D+D_ 12 M_

co. co- ] N e = E
I-M+ M_ J
and introducing (3)
E=0,

and the force vanishes with vanishing charge.

I f i n e q u a t i o n ( 1 0 ) w e let

--a = cp coefficient,

b=L " ,

c = constant term,

xz~,
Xo~,
then we may put:
X= Xo-+-A,

w h e r e A is a s m a l l q u a n t i t y . T h e n x 3 - - a x ~ = - - ( b x + c) .
I n t a k i n g x ---- a w e h a v e a s s u m e d - - ( b x ~ c) t o b e n e g l i g i b l e . I f w e
d i f f e r e n t i a t e x ~ - - a x ~ a t x = a = Xo, w e g e t ( 3 x J - - 2 a x o ) A x , a n d
to o b t a i n a s o l u t i o n o f e q u a t i o n ( 1 0 ) m o r e e x a c t t h a n t h a t g i v e n b y
( 1 1 ) w e m u s t s e t t h i s i n c r e m e n t e q u a l to - - ( b x + c) = - - a b - - b A
--c. (3Xo ' ~ - 2 a x o ) A = ( 3 a ~ - 2 a ~) A = a ~A = - - a b - - b A - - c .
a b -~- c
A--
a2 4:_b 9
For
M+= 1 ; M_----10 s ;
D+----10 .7 ; D _ = 1 0 .9 ;
q+=10-5 ; q-----10-7 ;
r 9 - - - - 1 0 -~ ; p= 4.73.1012
co~=10 -5 ; co-=10 -7 ;
and
a = 1 . 3 5 . 1 0 -5
b ---- - - 5 . 10 -15
c ---- 4 . 5 . 1 0 --~2

t h e n A+ = 4. - 10 -l~ a p p r o x i m a t e l y .
For the negative ions
15'6 MATHEMATICAL BIOPHYSICS

a = 1 . 3 5 . 1 0 .3 ,
b ---- - - 3 . , 1 0 -17 ,
c -= 2 . 10 .20 ,
and A_ = 1. 9 10 -14 approximately.
E is then equal to

o ~zr~ M+ M_
or about 4.8 9 10 -4 E.S.U. on the whole cell. This is sufficient to ac-
count f o r the observed charges on a cell (M.B., p. 126) y e t it can be
seen t h a t it does not affect the diffusion g r a d i e n t s w i t h i n the limits
o f experimental error.
We m a y conclude therefore, t h a t in a spherical cell the accumu-
lation of a charge on a cell by selection of ions of different charge
t h r o u g h different diffusion rates does not m a t e r i a l l y affect diffusion
gradients or forces. We have also shown t h a t an appreciable charge
can be produced by metabolism using reasonable values of the con-
s t a n t s of a cell. This m a y account f o r the charges t h a t vanish with
death of the cell as contrasted with charges produced by a Donnan
equilibrium in the membrane, which would not vanish at death.
In the special ease j u s t considered where h ---- De ---- o9, the molar
concentrations of the ions are identical at the surface, and since only
a v e r a g e (linear) gradients are considered, any differences in molar
concentrations will have the same sign t h r o u g h o u t the cell ; i.e., either
c+/M§ >_ c_/M_ f o r every r _< ro or c§247 <_ c~/M_. On the other hand,
if De and (or) h are finite, the molar concentrations need not be the
same at the surface, and e~/M§ X e_/M_, depending on r . This could
produce a change in sign of the local charges as different regions are
considered. The average charge m a y then be very small, but large
local charges m a y exist which m i g h t create local forces of importance
(in nuclear division, mitosis, protoplasmic streaming, or nerve excita-
tion and conduction). Since these effects are of a purely local n a t u r e
and since in the work t h a t has been done previously (Young, 1939;
Rashevsky, 1939) only average gradients, concentrations, and forces
have been considered, the possibility of s t r o n g localized effects does
not in a n y w a y affect the work of the past. The gross features of
cellular mechanics will remain unchanged, and such considerations of
local electrical forces need be made only when considering phenomena
o f a localized nature. The possible application of these local forces to
such phenomena as nerve excitation and conduction will be discussed
in the future.
The a u t h o r should like to acknowledge his indebtedness t o Dr: N.
 ROBERT R. WILLIAMSON 157

Rashevsky for suggesting this problem and for frequent helpful sug-
gestions that have contributed materially to the paper, and to Dr. A.
S. Householder for checking and correcting the manuscript.
This investigation has been aided in part by a grant from the
Rockefeller Foundation to the University of Chicago.
LITERATURE
Rashevsky, N., (1935) Physics 6, 33.
Rashevsky, N., (1938) Mathematical Biophysics, Physicamathematical Founda-
tions of Biology. Chicago: The University of Chicago Press.
Rashevsky, N. 1939. "The Mechanism of Cell Division." Bull. Math. Biophysics,
1, 23-30.
Rashevsky, N. 1939. "Mathematical Biophysics of the Cell with Reference to the
Contractility of Tissues and Amoeboid Movements." Bull. Math. Biophysics,
1, 47-62.
Young, Gale. 1939. "On the Mechanics of Viscous Bodies and Elongation in Ellip-
soidal Cells." Bull. Math. Biophysics, 1, 31-46.