Chemical Physics Letters 432 (2006) 548–552

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Computer simulation of magnetic properties of human blood

Mario E. Cano a, Alejandro Gil-Villegas a,*, Modesto A. Sosa a,
Julio C. Villagómez b, Oswaldo Baffa c
a
Instituto de Fı́sica, Universidad de Guanajuato, Loma del Bosque 103, Col. Lomas del Campestre, 37150 León, Guanajuato, Mexico
b
Instituto de Investigaciones en Biologı́a Experimental, Facultad de Quı́mica, Universidad de Guanajuato, 36050 Guanajuato, Mexico
c
Departamento de Fı́sica e Matemática-FFCLRP-Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP, Brazil

Received 31 August 2006; in final form 26 October 2006

Available online 6 November 2006

Abstract

The magnetic susceptibility of deoxygenated human red blood cell (RBC) is determined by Monte Carlo computer simulations using a
primitive model comprised of a hard-spheres fluid with magnetic central point dipoles in presence of an external magnetic field. Two
variations of this primitive model are considered. In the first case, a dipolar hard sphere describes a RBC, whereas in the second case
it represents a reduced hemoglobin molecule. The magnetic susceptibility is obtained from the observed linear correlation between
the magnetization and the external magnetic field. Very good agreement with experimental values is obtained for the second model.
 2006 Elsevier B.V. All rights reserved.

1. Introduction observed diamagnetic orientation of red blood cells under

Red blood cells contain hemoglobin, which is an iron-
containing protein capable of binding oxygen molecules.
The molecular structural configuration of the hemoglobin
strongly depends on the presence of oxygen. The hemoglo-
bin containing oxygen is called oxyhemoglobin, otherwise
is called deoxyhemoglobin. These structural features give
rise to the magnetic properties of red cells.
Since the pioneering work by Pauling and Coryell [1] on
the magnetic susceptibility of blood, many investigations
have reported both the magnetic properties and the influ-
ence of an external magnetic field on blood. Cerdonio
et al. [2] measured the magnetic properties of oxy- and car-
bon-monoxyhemoglobin at room-temperature, founding a
diamagnetic behaviour in both cases. Cerdonio et al. [3]
reported a molar paramagnetic susceptibility of
3000 mol/ml. Higashi et al. [4] studied the orientation of
erythrocytes in an 8 T static magnetic field, founding that
erythrocytes are oriented with the plane of their disk paral-
lel to the direction of the magnetic field. Yamagishi et al. [5]
*
Corresponding author. Fax: +52 4777885100x8410.
E-mail address: gil@fisica.ugto.mx (A. Gil-Villegas).
the application of a high magnetic field. Shalygin et al.
[6] studied the behaviour of erythrocytes under strong mag-
netic field gradients. These authors reported a susceptibility
for diamagnetic erythrocytes of (0.13–0.65) · 108 cgs
emu/cm3 Oe and (13–33) · 108 cgs emu/cm3 Oe for para-
magnetic erythrocytes. Nakano et al. [7] have also reported
the effect of a magnetic field on the erythrocyte rotation.
A precise knowledge of the magnetic properties of human
blood is required for an accurate modelling of functional
magnetic resonance imaging. fMRI is sensitive to changes
in the oxygen content in blood. Spees et al. [8] determined
relaxation parameters of blood and found a magnetic sus-
ceptibility difference between fully deoxygenated and fully
oxygenated red blood cells at 37 C of 0.27 ppm, as deter-
mined independently by MR and superconducting quantum
interference device (SQUID) measurement.
From the point of view of the modelling of biological
systems it is important to determine which are the basic
molecular features that are necessary for a proper model-
ling. Over the years, primitive models have been very useful
in the modelling of complex fluids by computer simulations
[9]. In this Letter, we address the description of the mag-
netic susceptibility of blood using a primitive model com-

0009-2614/$ - see front matter  2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.cplett.2006.11.003
 M.E. Cano et al. / Chemical Physics Letters 432 (2006) 548–552
prised of a dipolar hard-spheres fluid (DHS) in the pres-
ence of a external field. We study two variations of this
model, depending on the physical values used to reproduce
the magnetic behaviour of human blood, either red blood
cells or reduced hemoglobin molecules.
2. Computer simulation of dipolar particles using free
boundary conditions
As a consequence of the long range nature of dipolar inter-
actions, the properties of polar fluids are very different from
substances formed by molecules interacting by van der Waals
forces. The standard method used in computer simulation of
non-polar systems uses a periodically replicated simulation
cell of length L containing N particles [10]. Interactions
between particles are treated by the minimum image conven-
tion. This method will be denoted as free boundary conditions
(FBC) method. In the case of systems with long-range interac-
tions, the number of interacting particles separated by several
L distances could be non-negligible. Since L grows as N1/3, the
simulation-cell volume can be increased sufficiently enough to
contain K by increasing the number of particles, and the use of
the FBC method is justified.
In our study of the magnetic properties of human blood,
we considered a system of N hard spheres (HS) of diameter
r with a point dipole p = pe at the center of the sphere,
where e denotes a unit vector and p is the magnitude of
the dipolar moment. Under the FBC approximation, the
interaction between a pair of particles is given by
uðr; X1 ; X2 Þ ¼ /HS ðrÞ þ /DD ðr; X1 ; X2 Þ;
where r is the relative positional vector between the centers
of a pair of hard spheres of diameter r, X1 and X2 are the
dipoles orientations for particles 1 and 2, respectively, and
/HS and /DD are the hard-spheres and dipole–dipole
potentials given respectively by

1 if r < r;
/HS ðrÞ ¼ ð2Þ
0 if r P r;
and
p2
/ðr; X1 ; X2 Þ ¼  ½3ð^r  e1 Þð^r  e2 Þ  ðe1  e2 Þ;
r3
where ^r is a unit vector and r ¼ r^r.
In the presence of an external magnetic field H, the
potential energy of the system is given by
X
N X
N X
N and vd = 0.6 vwater = 5.4 · 106. The susceptibility of
U¼ /ðr; X1 ; X2 Þ  p e  H:
i< j i¼1
The magnetic response of the fluid due to the presence of
the external field is obtained from the standard relation
M ¼ vH;
where M is the magnetization induced in the fluid by H and
v is the magnetic susceptibility. The magnetization is calcu-
lated as
549
1 X N
M¼ pei ; ð6Þ
L3 i¼1
i.e., the magnetic dipolar moment per volume of the simu-
lation cell.
3. Models and results
Two different models were considered, using a hard-
spheres fluid carrying magnetic central point dipoles in
the presence of an external magnetic field H parallel at
the k axis. In model I, the HS diameter and dipolar
moment are given by the respective values of a red cell.
In model II, the diameter and dipolar moment of a reduced
hemoglobin molecule were used. The main difference
between both models is the way in which the carriers of
the dipolar moment inside the blood is considered. In the
first case the fluid is identified with a fluid of red blood
cells, whereas in the second case this representation is chan-
ged to a fluid of hemoglobin molecules.
In both cases, the magnetic properties of human blood
were obtained using computer simulations with the Monte
Carlo (MC) method under the FBC approach. The DHS
fluid is contained within a cubic simulation cell with length
L in the presence of a constant external magnetic field H,
whose potential energy is given by Eq. (4). Simulations
were carried out using a NVT ensemble according to the
Metropolis scheme [11]. The magnetic susceptibility is
obtained from the simulated values of the magnetization
ð1Þ M as the external magnetic field H varies, applying Eq.
(5). We explain now the procedure followed for both
models.
3.1. Model I
Following Ref. [8], we are going to consider the suscep-
tibility per ml of substance. The magnetic susceptibility for
whole blood, v, is given by
v ¼ mp vp þ m d vd ; ð7Þ
where vp and vd are the paramagnetic and diamagnetic sus-
ð3Þ ceptibility contributions, and mp and md are their fractions,
respectively. The paramagnetic contribution arises from
the deoxyhemoglobin, whereas the diamagnetic term is
basically given by the susceptibility of water molecules,
since 60% of blood solution is water [8]. Then, md  0.6
ð4Þ whole human blood is v = 3.5 · 106 [12]. Using these re-
sults in Eq. (7), an estimated value for vp is obtained,
vp  2:2  105 : ð8Þ
This value agrees with reported data of vp, that has been
ð5Þ
determined within the range  6.07 · 106 6 vp 6 2.2 ·
105 [8,12–17]. Since
vp ¼ nRC vRC ð9Þ
550 M.E. Cano et al. / Chemical Physics Letters 432 (2006) 548–552

Fig. 1. MC simulated values for the magnetization M of a DHS fluid in the presence of an external field H for models I (a) and II (b). Results correspond
108, 256 and 500 particles. Lines are linear least-square fits for each simulated system.

where nRC is the number of red cells contained within 1 ml (5.7 ± 0.2) · 104 and (5.7 ± 0.2) · 104 for 108, 256 and
of blood, nRC = 5 · 109 [18], and vRC is the magnetic sus- 500 particles, respectively. The proper thermodynamic
ceptibility of a red blood cell, the magnetic susceptibility value of vp could be obtained by extrapolation in the limit
of a red blood cell is obtained using Eqs. (8) and (9), N1 ! 0. From a linear extrapolation, it results
vp = 6.4 · 104, that is a value higher than the experimen-
vRC  5  1015 : ð10Þ
tal data by at least a factor of 20.
According to Eq. (5), the magnetization M of a RBC due
to the effect of an external magnetic field H is given by 3.2. Model II
M ¼ vRC H: ð11Þ
In Model II, the magnetic properties of human blood
Assuming that the magnetization M is basically given by are described by a fluid of reduced hemoglobin molecules.
the dipolar moment of the cell, lRC, i.e. Using reported experimental values for the dipolar moment
M ¼ lRC =V RC ; ð12Þ and X-ray crystallographic effective diameter of this mole-
where VRC is the volume occupied by a RBC,
VRC = 9.0 · 1011 ml [18], then Eqs. (10)–(12) enable us
to have a estimated value of lRC,
lRC  4:5  1031 H: ð13Þ
In terms of the magnetic field intensity B = l0H, where
l0 = 4p · 107 Tm/A is the magnetic permeability in vac-
uum, Eq. (13) can be rewritten as
lRC  3:4B  1025 ; ð14Þ
2
where the units of lRC are A m .
In Model I, the diameter of a DHS particle is obtained
from VRC and its dipolar moment from Eq. (14). Simula-
tions were performed for a temperature T = 300 K and
for a concentration nRC = 5 · 109 cells/cm3. Independently
of the number of particles used in the simulations, the mag-
netization M changed linearly with the external field H. In
Fig. 1-a we report this behaviour for the cases of 108, 256 Fig. 2. Magnetic susceptibility as a function of the inverse of the number
and 500 particles, where the systematic dependence of the of particles (N1) for a dipolar hard-spheres fluid (model II), obtained
from MC simulated values for the magnetization of a DHS fluid in the
results tends to reduce as the number of particles increases.
presence of an external field. Line in dots is a linear least-square fit; solid
The magnetic susceptibility vp was calculated as the slope line is the experimental value given by Sakhnini and Khuzaie [17], and
of the straight line fitted to the simulation data M versus dashed line is the theoretical prediction according to the Langevin–
H. The obtained values for vp are (4.0 ± 0.20) · 104, Brillouin model.
 M.E. Cano et al. / Chemical Physics Letters 432 (2006) 548–552 551

Table 1
Values of the simulated values of the magnetic susceptibility, vp, and molecular parameters for a system of dipolar hard spheres representing a fluid of red
blood cells (Model I) and a fluid of reduced hemoglobin molecules (Model II)
Model Dipolar moment (A m2) HS diameter (nm) Magnetic susceptibility (MC) Magnetic susceptibility (Experiment)
I 3.4 B · 1025 5560.1 6.4 · 104 6.07 · 106 6 vp 6 2.2 · 105
II 7.416 · 1023 6.4 7.5 · 107 7.33 · 107
The predicted susceptibilities for both models are compared with the experimental values, as explained in the text.

cule (7.416 · 1023 A m2 [17] and 6.4 nm [19], respectively), where lRF and l0 are the magnetic permeability for the
the magnetization of a DHS fluid at temperature continuum surrounding the spherical cavity and vacuum,
T = 300 K and concentration nHRB = 2.67 · 108 RHB mol- respectively. Due to the magnetizable cavity, the external
ecules per red cell was studied (Fig. 1b). Using the simu- field that must be considered in Eq. (4) is the field produced
lated values of vp for different number of particles, an inside the cavity Hc, i.e.
extrapolated value can be obtained in the thermodynamic
9lRF l0
limit N1 ! 0, obtaining vp = 7.5 · 107 (Fig. 2). From Hc ¼ H; ð16Þ
the magnetization curves of erythrocytes under a static ðlRF þ 2l0 Þð2lRF þ l0 Þ
magnetic field, Sakhnini and Khuzaie [17] determined that These equations can be applied if we know the value of the
vp = 7.33 · 107, which is very close to the Langevin–Brill- magnetic permeability of the surrounding media, lRF.
l2
ouin theoretical prediction, vp ¼ N3kT ¼ 7:49  107 . Model However, since
II improves notably the accuracy of the MC simulated pre-
l ¼ l0 ð1 þ vÞ; ð17Þ
diction. In Table 1 we summarize the results described in
6
this section. and v  10 for human blood, then lRF  l0, and from
Eq. (16) Hc = H. Then the Reaction-Field expressions re-
duce to the FBC equations.
4. Reaction-Field method

The simulation of dipolar systems under the FBC 5. Conclusions

approach can be justified if the simulation cell is large enough
in order to include the volume of interactions per particle,
otherwise we have to use special methods such as the Ewald
sum or the Reaction-Field method (RF) [10]. More recently,
a novel method developed by Wolf et al. [20,21] has been
applied in the study of ionic systems with a significant gain
in computing time The Wolf method has also been applied
to colloidal [22] and multipolar fluids [23].
We will discuss here the correction introduced to the
FBC results using the RF method, that has been proved
to predict accurately properties of complex fluids [24,25].
This method, developed by Onsager [26] and applied for
the first time in computer simulations by Barker and Watts
[27], considers that each particle can be surrounded by a
spherical cavity of radius R. All the other particles con-
tained within the cavity interact with the central particle
via the bare dipole–dipole potential, Eqs. (1)–(3), whereas
the particles that are outside the cavity are treated as a
dielectric continuum that is polarized by all the particles
inside the cavity. The procedure can be also applied to
magnetic systems due to the equivalence between the mag-
netostatic and electrostatic equations [28]. The electrostatic
pair effective potential for the Reaction-Field method [29]
can be transformed to the magnetic system,
In this Letter, we have presented the use of a very sim-
plified primitive model to describe magnetic properties of
human blood. Studying the magnetization curves of a dipo-
lar HS fluid under the effect of an external magnetic field,
we have determined the magnetic susceptibility for two
modelling cases: a fluid formed by red cells, or by reduced
hemoglobin molecules. We have found that the magnetic
susceptibility of human blood is predicted an order of mag-
nitude higher in the case of modelling red cells, and is pre-
dicted very accurately in the case of reduced hemoglobin
molecules.
Acknowledgement
This work was supported by CONACyT (Grants 38749-
E and 41678-F).
References
[1] L. Pauling, C.D. Coryell, Proc. Natl. Acad. Sci. USA 22 (1936) 210.
[2] M. Cerdonio, A. Congiu-Castellano, L. Calabrese, S. Morante, B.
Pispisa, S. Vitale, Proc. Natl. Acad. Sci. USA 75 (1978) 4916.

( 2
 2
lRF l0
 pr3 ½3ð^r  e1 Þð^r  e2 Þ  ðe1  e2 Þ  2 p
R3 2lRF þl0
e1  e2 if r < R
/RF ðr; e1 ; e2 Þ ¼ ð15Þ
0 if r > R;
552 M.E. Cano et al. / Chemical Physics Letters 432 (2006) 548–552
[3] M. Cerdonio, S. Morante, S. Vitale, Method. Enzymol. 76 (1981) 354.
[4] T. Higashi, A. Yamagishi, T. Takeuchi, N. Kawaguchi, S. Sagawa, S.
Onishi, J. Blood 82 (1993) 1328.
[5] A. Yamagishi, T. Takeuchi, Physika 177 (1992) 523.
[6] A.N. Shalygin, S.B. Norina, E.I. Kondorsky, J. Magn. Magn. Mater.
31 (1983).
[7] N. Nakano, J. Ostuka, A. Tasaki, Biochim. Biophys. Acta 278 (1972)
355.
[8] W.M. Spees, D.A. Yablonskiy, M.C. Oswood, J.J.H. Ackerman,
Magnet. Reson. Med. 45 (2001) 533.
[9] D. Frenkel, B. Smit, Understanding Molecular Simulation, Academic
Press, 1996.
[10] M.P. Allen, D.J. Tildeslay, Computer Simulation of Liquids, Oxford
Science Publications, 1987.
[11] N. Metropolis, A.W. Rosenblueth, M.N. Rosenbluth, A.H. Teller, J.
Chem. Phys. 21 (1953) 1087.
[12] Y. Haik, V. Pai, C.J. Chen, J. Magn. Magn. Mater. 194 (1999) 254.
[13] D. Melville, F. Paul, S. Roath, IEEE Trans. Magn. 11 (1975) 1701.
[14] M. Zborowsk, G.R. Ostera, L.R. Moore, S. Milliron, J.J. Chalmers,
A.N. Schechter, Biophys. J. 84 (2003) 2638.
[15] C.S. Owen, J. Appl. Phys. 53 (1992) 3884.
[16] M. Takayasu, D.R. Kelland, J.V. Minervini, F.J. Friedlaender, S.R.
Ash, in: Proceedings of the International Workshop on Chemical
Physics and Biological Processes under High Magnetic Fields, 1999.
[17] L. Sakhnini, R. Khuzaie, Eur. Biophys. J. 30 (2001) 467.
[18] A.C. Guyton, J.E. Hall, Textbook of Medical Physiology, W.B.
Saunders Co, 1996.
[19] L. Sakhnini, J. Appl. Phys. 93 (2003) 6721.
[20] D. Wolf, Phys. Rev. Lett. 68 (1992) 3315.
[21] D. Wolf, P. Keblinnski, S.R. Philipot, J. Eggebrecht, J. Chem. Phys.
110 (1999) 8254.
[22] C. Avendaño C, A. Gil-Villegas, Mol. Phys. 104 (2006) 1475.
[23] C. Avendaño, N. Ibarra-Ávalos, C.M. Quezada, J. Medina, A. Gil-
Villegas, Rev. Mex. Fis. (in press).
[24] A. Gil-Villegas, S.C. McGrother, G. Jackson, Mol. Phys. 92 (1997)
723.
[25] S.C. McGrother, A. Gil-Villegas, G. Jackson, Mol. Phys. 95 (1998)
657.
[26] L. Onsager, J. Am. Chem. Soc. 58 (1936) 1486.
[27] J.A. Barker, O.R. Watts, Chem. Phys. Lett. 3 (1969) 144.
[28] D.J. Jackson, Classical Electrodynamics, Wiley & Sons, 1975.
[29] M. Neumann, O. Steinhauser, S.G. Pawley, Mol. Phys. 1 (1984) 97.