(parallel-aligned), and of spin-glass type.

Each of the above structures exists under different conditions of temperature, electric field, MAP distribution, and MT length giving rise to a possible sensitive state-switching mechanism. The ferroelectric state appears to be most suitable for assembly I disassembly processeswhile the spin-glass state is ideally suited for information processing(and thus can be seenas providing the substrate for consciousness) will be argued in this paper. as THE EMERGENCEOF DIPOLAR PHASES Our basicpremise is that the entire MT may be physically viewed as a regular (triangular) array of coupled local dipole moments that interact with their immediate neighbors via dipole-dipole forces. Although Melki et al. (1989) showed that tubulin undergoes a conformational change (Figure 30.2a),we will tentatively adopt a simplified view where elastic degreesof freedom are not explicitly incJuded in the description. However, an appropriate generalization of the physical model poses no technical difficulties and we comment on it in the last section. The starting point in the analysis is to adopt a triangular lattice Structure (located on the surface of the MT) with the dimensions and orientations as shown in Figure 30.2b and 30.2c.Each lattice site is assumed to possessa dipole moment p = Q .dwhere Q = 2 eand d = 4 nm and its projection on the

japted from Amos and

I1gperiod an MT sudalled a rescue). :1izedwhich leads to 1d Mandelkow 1992). :ormation processing nett (1987)suggested ISinformation strings structural similarity tecture is quite strik~ -ansferring 1tS of the cell interior rallel arrays

Alpha

d:
~

e -

r""-. Beta

State

State

(a)

~ #e

4.9nm

-..,

8nm

Jz

5ioned as playing the

c.

~e r 1- .rij

e emergence

of

con-

I--f 5nm

s ground-state propnts of dipoles we see ectric), ferroelectric

(b)

(c)

Figure 30.2 A graphical description of the structural units in a microtubule: (a) the two electronic states of a dimmer,(b) the dimensions and angles of a unit cell, and (c) a schematic illustration of the model parameters used and their meaning.

409

Tuszyrtski et al.: Microtubular Self-Organization

vertical axis can only be + p or -p. The interaction (dipole-dipole) energyE.. between two neighboring lattice sites (labelled i and j). is, therefore, 'I
1 3cos2(j-l

Ejj=

47rEE

.. '1

p2

(1)

where EO the vacuum permitivity, e the dielectric constant of the medium, is rij is the distance between sites i and j. The angle 6 is between the dipole axis and the direction joining the two neighboring dipoles. Figure 30.3 illustrates the relevant situation used in our calculations. In Figure 30.3athe signs " + " and" -" refer to dipole-dipole interactions that prefer either a parallel or an antiparallel arrangement of dipole moments, respectively. The numerical results for the constants/1' /2' and /3 and the corresponding angles that were found based on the known structural data (Rasmussenet al. 1990)are:h = 5,77 .10-21/,/2 = --0.71 .10-21/, !3 = 3.40.10-21 /,61 = 0,62 = 58.2, and 6; = 45.6. With the known strong axial anisotropy of interactions we can map this situation onto an anisotropic two--dimensional Ising model on a triangular lattice so that the approximate effective Hamiltonian is now given by (2) and the effective spin variable Siz= :t1 denotes the dipole's projection on the vertical MT axis. The exchange constants lij take the values /1, 12,13 depending on the choice of dipole pairs. Due to the fact that 12 < O and that there are an odd number (13) of protofilaments, the system exhibits a certain amount of frustration (Suzuki 1977).This means that for a closed path along the direction corresponding to 12,it is impossible to satisfy all bond requirements. Hence, there will always be a conflict (hence the word frustration) between satisfying the energetical requirements of " + " bonds and " -" bonds. The ensuing dipolar phase structure is known in the physical literature as a spin-glassphase (Fischer 1983, 1985). In a spin-glass (SG), spin orientations are locally "frozen" in random directions due to the fact that the ground state has a multitude of equivalent orientations. For example, for eachtriangle reversing the spin on one side with respectto the remaining two, leads to an energetically equivalent configuration. Having the number of triangles on the order of the number of lattice sites, that is, N -2 .104,yields the degeneracy of the ground state on the order of ~ which is a very large number! This provides a very convenient property from the point of view of encoding information in such a highly degenerate dipolar lattice state. Note, however, that the other two directions do not exhibit frustration and this limits the extent of the SG phase. Relatively small potential barriers separating the various equivalent arrangements of spins in the SG phase may playa very useful role since relaxation times are very long for the various accessiblestates.Someother properties of the spin-glass phase are the absence of long-range order
410 Tuszyliski et al.: Microtubular Self-Organization

411

:i is longle state to the small ion of the eld along sufficient :hat fields quite feaature will tlso sensi'presence the tem"acterized ons along .rocessing najor role
-nski, and in the F ! range of

perature lies between 200K and 400K indicating the possibility of the associated phase transition close to room temperature, that is, at physiological conditions. Many important factors may affect the value of Tc and thus provide sensitive control mechanisms for phase selection. Through a coupling to the elastic degreesof freedom (conformational change),the dielectric constant E may be altered by the presenceof water molecules surrounding an MT structure thereby decreasing the value of Tc and introducing dipolar disorder. Small structural changes,in particular shifts in the angles between the diller dipoles, may remove the frustration mechanism effectively preventing the onset of the SG phase. Changes in the opposite direction can enhancefrustration favoring the SG over the F-phaseeffectively switching from the growth mode of operation of MTs to their information-processing behavior. In order to obtain some insight into the above questions, we have performed Monte--Carlo simulations for finite lattices with dimension 13 X N (N is the length of the microtubule in terms of the number of layers). It is clear that as N increases,the SG phase is gradually removed. We see this effect by directly plotting the mean polarization per site for N = 26 (Figure 30.3a)and N = 5000(Figure 30.3b)as two contrasting examples. We conclude that dynamic processesleading to the elongation of MTs could effectively remove the information processing capabilities of MTs by expelling the SG phase. The same can be achieved by raising the temperature above a characteristic value that is length dependent. We have also examined the effect of external electric fields and MAPs on the aforementioned transition. The electric field shifts the transition region and makes it broader. A similar effect can be seenby incorporating MAPs as "empty" (that is, non-polar) lattice sites. The actual magnitude of the shift and broadening depends on the pattern of MAPs chosenand the ratio of MAPs to the total number of lattice sites. Taking the set of parameter values which yields Tc = (300 :!:15) K for the perfect lattice results in Tc = (250:!:20)K for the lattice with MAPs at a ratio of 1:11while Tc = (230:!:20) K is obtained for a ratio of 1:8. This indicates that MAPs substantially lower the transition temperature and make the SG-phaseaccessibleto the MT system at much lower temperatures than those required in the absence of MAPs.

mation

Nards ;ation of a -erred end the MT at

he various n the conlIning that 5 the most nce to the nfinite trionly two below Tc), lat the critthe combile realistic ,itir !n tem-

INFORMATION

CAPACITY ESTIMATES

In order to examine the usefulness of MTs as the cell's information processorswe must first evaluate the information capacity within each of the three phases identified. These results can be used to find the optimal conditions for the MTs to function as the substrate for consciousnessrelated activities. We base the calculations that follow on the standard

413

Tuszyriski et al.: Microtubular Self-Organization

(Shannon) definition 1990)

of information

I of a statistical system where (Haken

K I = -2 ;=1 Here, Pi stands for a probability bility distribution must satisfy: value in state i and, obviously, the probap;ln{p;) {3)

I Pi = 1 with O ~ Pi ~ 1.

(4)

For the ferroelectric and paraelectricphases adopt the mean-field approxwe imation where eachstateis characterizedby the continuous variable p (mean polarization per site). The energy functional is taken in the Landau form as E = ( ~p2
2

+ ~p4 ) N 4

(5)

where No is the total number of sites in the lattice, A = a(T-T J and B > 0. As is well-known above the critical temperature, that is, for T > Tc' E is minimized by P = 0 while below the critical temperature, that is, for T < Tc by P:!: = :t(-A!B)l/2. The associated continuous probability distribution f(P) that replaces Pi of Equation 3 is the Boltzmann-weighted tion in the form: distribution func-

.f(P) = 2-1exp( -{3E) = foexp(aP2-yp4)

(6)

where fo = 2-1 is the normalization, ~1 = kB T, a = -A/(2 kB T) and y = B/(4 kB T). Hence, for T > Tc'f(P) is single-peakedat P = 0 while for T < Tc it is double-peaked at P = Pt. Following Haken (1990) we calculate the information capacity in the paraelectric (P = 0) and ferroelectric (P * 0) phasesas I = In(2) -a(P2) + y(p4) where the averagesare obtained using: (pn) = fOO .f(p)pndP -00 (8) (7)

We carry out the requisite calculationsin a straightforward manner for both the ferroelectric and paraelectric phaseswhere analytical calculations can be performed. For the SG-phase,however, we assumethat the above prescription is valid only within the local domain of coherenceor within the correlation length. Hence,for eachdomain i we have a local polarization pi and the associatedprobability distribution fi(P i), essentially analogously to those of Equations 5 and 6. Thus, for the total system the probability distribution becomesa product of local distributions eachof which characterizes a domain of coherence

415 414 Tuszyriski et al.: Microtubular Self-Organization

ere (Haken

n f = lltj(Fj) j=l

(9)

where n is the number of domains. Note that n depends on temperature and we assumefor simplicity that (3)
n = 1 +~ol)(TT B) (10)

the probaTA-TB in order to interpolate continuously between the ferroelectric and paraelectric phases since T B :s; T:s; TAoAt T = T B' virtually the entire system is uniformly polarized while at T = TA it is completely depolarized and incoherent. Note, that as a consequence of Equation 9 we obtain for the information capacity in the SG-phase

(4)
celd approxble p (mean iau form as

n I = I Ii i=l

(11)

(5)
) and Tc'Eis )rT B > 0. min-

<Tcby j(P) func-

"ibution Jution

where 4 refers to each individual domain. Our numerical computation clearly indicates that information capacity I is highest at the boundary between the SGand the paraelectricphase(seeFigure 30.4)and hence if MTs are to be effective as information processors,they should use this.narrow "window of opportunity" at the border area between these two phases.Of course, the actual location of the border area depends on the magnitude of the electric field applied and the concentrationof MAPs present.
SUMMARY AND OUTLOOK

(6) .T) le and for 'Y = T < Tc

We have argued in this paper that the spatial arrangement

of dipole

moments of a MT is crucial to its functioning as a dynamic self-organizing

lacity

in the

(7)

600(
500
d 400 o .= tIS 300 :B 200 100

Paraelectric

Spin Glass Ferroelectric

40
-l00L TB TA

Temperature (K)
Figure 30.4 Plot of the information capacity as a function of temperature.

415

Tu8zynski et al.: Microtubular Self-Organization

system. Due to the presenceof frustration in the dipole-dipole interactions, a SG phase is predicted to arise at low enough temperatures and electric fields. The presenceof MAPs will lower the temperature values required for SG-formation. The transition temperature itself decreases proportion in to the MAP ratio. The attractivenessof the SG phase has been recognized earlier (Stein 1992)and in the present context it lies in its maximum computational capabilities offered by a highly degenerateground state. Moreover, long relaxation times give relative stability to short-range correlated dipole patterns. Each pattern can be seenas containing binary information encoded in the lattice. The other ordered statethat is possible to exist is a F phasewith an almost perfect alignment of dipole moments along the protofilament axis. It is characterizedby long-range order and henceits usefulnessfor information transfer and processing is dubious. However, it eagerly supports the formation of domain walls between the two stable orientations of dipole moments. The application of an external electric field preferentially directs kink-like excitation towards the properly aligned end causing a disassembly of the protofilament due to the energy releasedby the kink. Wehave recently performed preliminary calculations including the presence of a conformational change associatedwith a f3-state.We have found using Monte Carlo simulations that quite a different picture arises.Instead of three dielectric phases,only two exist: a low-temperature F phase and a high-temperature ferri-electric phase. The latter phase is characterizedby the formation of local domains of polarization in two possible directions: vertically up the MTs axis or downwards and at 29 ooff the axis. However, net polarization appears to persist well above room temperature. The polarization may be a key physical factor in the hypothesized communication between microtubules in sufficiently concentratedassemblies. We have discussed the various possible control mechanisms (field, distortion, temperature, MAP patterns) that could provide a means by which the MT could select an operating mode between information processing and assembly/ disassembly types. This could shed some light on why the MT formation rate is enhanced in particularly important stages of the organism's history and development (learning, division, growth).

ACKNOWLEDGMENTS
Th~sresearchwas supported by NSERC(Canada),DAAD, and the Alexander yon Humboldt Foundation.
REFERENCES Amos, L.A., and A. Klug. 1974.Arrangement of subunits in flagellar microtubules. I. Cell Sri. 14:523-50.

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Tuszyrlski et al.: Microtubular Self-Organization

nteractions, md electric es required proportion recOgnized mum corntate. More.correlated ~formation 1an almost t axis. It is lformation rts the forof dipole llly directs disassem9 the presave found ~s.Instead 1aseand a terized by jirections: However, lture. The mmunica~s. field, disby which Irocessing 1 why the ;es of the

Athenstaedt, H. 1974.Pyroelectric and piezoelectric properties of vrtebrates.Ann. N. y: Acad. Sci. 238:68-93. Bamett, M. 1987. Molecular systems to process analog and digital data associatively. Proceedings the Third Molecular ElectronicDeviceConference, of edited by F. Carter. Washington, DC: Naval ReseachLaboratory. Dustin, P. 1984.Microtubules.Berlin: Springer. Fischer, K. H. 1983.Spin glasses(I). Phys.Stat. Sol. (b) 116:357. Fischer, K. H. 1985.Spin glasses(II). Phys.Stat. Sol.(b) 130:13. Haken, H. 1990.Synergetics: introduction. Berlin: Springer-Verlag. An Hameroff, S. 1987. Ultimate computing:Biomolecular consciousness nanotechnoland ogy. Amsterdam: North Holland. Hameroff, S. R., and R. C. Watt. 1982. Information processing in microtubules. I. Theor.Bioi. 98:549-61. Horio, T., and H. Hotani. 1986.Visualization of the dynamic instability of individual microtubules by dark-field microscopy. Nature 321:605-07.
Mandelkow, E. M., and E. Mandelkow. and the Cytoskeleton 22:235-44. 1992. Microtubule oscillations. Cell Motility

Margulis, L., L. To, and D. Chase. 1978. Microtubules in prokaryotes. Science 200:1118-24. Melki, R., M. F. Carlier, D. Pantaloni, and S. N. Timasheff. 1989.Cold depolymerization of microtubules to double rings: Geometric stabilization of assemblies. Biochem.28:9143. Rasmussen,S., H. Karamppurwala, R. Vaidyanatu, K. Jensen,and S. R. Hameroff. 1990. Computational connectionism within neurons: A model of cytoskeletal automata subserving neural networks. Physica0142:428-49. Sataric', M. V., J. A. Tuszyrtski, and R. B. Zakula. 1993.Kinklike excitations as an energy transfer inversion in microtubules. Phys.Rev.E48:589. Stein, D. L., ed. 1992.Spin glasses biology.Singapore: World Scientific. and Suzuki, M. 1977. Phenomenological theory of spin-glasses and some rigorous results. Prog. Theor.Phys.58:1151.

e Alexan-

rotubules.

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Tuszyliski et al.: Microtubular

Self-Organization