Nunubiofogy 1992) J, 487-468 Acousto-conformational Transitions in Cytoskeletal Microtubules: Implications for Intracellular Information Processing ALEXEI SAMSONOVICH.'* ALWYN SCOTT! anp STUART HAMEROFF* ‘Applied Mathematics Program, University of Arizona, Tucson, AZ 85724, USA “Advanced Biotechnology Luboratory, Department of Anesthesiology, University of Arizona Medical Cerner, 1501 Novih Campbell Avenue, Tucson, AZ 85724, US The hspothesis of tong distance coherent, gigahert:-range excitations in the extoskeleton and thetr possible role in energv/nformation conversion tn living cells is supported by observations of gigakert=-range phonon excitations in proteins, shurp-resonant aon thermal effects of microwave eicetromagnetic irradiation on living cells and long-range regularities in evtoskeletal structures, such as ihe superlattice attachinent patterns of microndde associated proteins (MAPs) on micrombules. The latier ts usually treated in ters of conformational charges of snicrotubuele subunits, Usitg a Frohlich-tike model the presen werk mumerically confirms that these conformational changes cant be provoked by self localized coherent phonon excitations whose original speciran carries input information. The inherent phonon spectrunt of the structure is then dependent on MAP locations and cun fianetion in a memory storage capacity. Such a systent appears capable of adapiation and signal recogntion involving spectrum — structure retations with feedback learning rules. linplications inchule intracellular information processing and motecuiar level electronic devices based on confornuiional phase transitions i proiein arrays Keywords: Coheren excuatins. coherent phonons. evosketenn. Prahlict eXeitaions. fermen prevessurg. microidhales. molecular computing, prowin conformation, tabula NTRODUCTION ‘The existence of coherent, gigahertz-range oscillatory excitations in biomolecular structures and their possible role in living cells have been discussed in nunierous theoretical proposals inainly based on the Froblic (1968) or Dayydoe (1981. 1985} approaches ta connection with Gifferent components of Living cells: membranes. jadividial proteins. actin filaments, ete (Lor review see Frohlich, 1988: Frohlich & Kremer. 1983: Golant, 19891, Although supportive experiments! data are inconclusive, such organized excitations could explain a great deal regarding organization and information processing in living systems. Th the present paper we are Focussing. an the possibility of coherent excitagions in microtubules (MTs) (Hamerol!, 1987; Rasmussen ef af.. 1990). MIs are the primary components of the cycoskeleton intracellular networks of protein polymers which orchesirae cytoplasinie activites (Dusua, 1984, In contrast o other cytoskeletal elements, MTs have a non-trivial. periodic structure (Mandelkow ef af. 1986) und very tong persistent length, about gan (Dustin, 1984), ‘These should result in & spectrum of global phonon niodes, Corresponding patteras of standing waves in MTs can therefore be calculated im the 457488 AL SAMSUNOVICH 2 tr Tinear approximation from the syinmetsy of the structure (Figures | and 2, see Appendis tor details There are at least two lines of indirect experimental evidence for the existence of cabereat oscillatory phenomena in MT's within living cells: (Q) Neubuer eral. (1990) showed that 2.45 GH irradiation non-thermally activates M1 inediated pinoeytotic uptake in brain capillary endothelial cells Cblood —brain barrier function’) However. experimental data showing the elect directly at the molecular level ure lacking Cor general review of nonthermal microwave bioelivets. see Brown & Chattopadhyay. 1988: FIGURE: 1. (af) Experinventally observed patterns ot the MAP attachment sites on MTs Burns, LU78: Kim et af.. 1986), Some ot patterns (cand N exactly cuimede with patterns ot tie ed tite ‘calculated phone) mies main de ambi df ## Paticens a the ME phenom miokkes masini calculated seenrding to AU), Arrows at cach site eepresent the complex amplitude of the related propayating mode (47)ACOUSTO-CONFORMATION AL TRANSITIONS. 450 N m /\ N / eM Af 5 | ° | Bf 21) Viel of el t © Ope ee ee 0.0 0.2 0.4 0.6 o8 1.0 FIGURE 2 Paoswn spectrum ot the MP. calcula! severing (A UL. AAS) and [N99 for particular chuigg oF the coupling wonstants |ALD:, Frequency in GHz. buhels show positions at sone selected modes, represemed st Figure L Froilich, 1988; Golant, (9891, It is noteworthy that the action spectta of nonthenesd| micrawae efzets have Skerp resonant Lnes with the corresponding quality fuctor of the order of 10° 10° (Devsatkoy er af. 1973). This is difficult 10 understand in terms of biochemical reactions or noa-pumped near-equilibrium molecular vibrational excitations, because gully factors or molecular oscillatory modes are usually less than 10° ¢Sertkoy &¢ Khesophoroy. 1989 Gonbetg. 1991), However. lising systems are usually far from thermal equilibrium. We know that MTS consume biochemical energy via GTP hydrolysis and phoxphorylation, Hence. we ean assume a certain pumping mechanism, which can provide sel-excitation of molecular phonen'vibron modes, Thus we arrive at a Frihlich-like model. Gi) Other indirect evidence for aseilltiory phenomena in MTs includes the existence of microtubule associated protein (MAP) attachment site superlattices on MTs (Figure 1, a feature which is well established bur poorly understood (Rim cf a?.. 1986), The MAP attackmiem sites are MT tubulin subunits which differ from the others. apparently in their cenormutional state This superlattice appears to be regular at large distinces along the MTs. at fact difficult to- understand in terns of local rules of superlattice Formation iavolving static strains (Roth ef ad. 1970) or MT self-assembling niles, due to finite grobability of error Even more intriguing is the repularity of axopodial MT patterns (Cuchon & Cacbon, 1971, Bardele, 1977). One exaniple of such structure is shown in Pigure 3. The mechanism of moxphogenesis of these pallerns remaits unknown. Different variants of linking between Ms int MAP superlattices existing at the same time in the sume depending on thet position in the structure. Karlier romenological explanations hased on the grudion concept developed by Roth er a. (1970) involved graded conformational changes in MTs induced by stale mechanical strains, but appeared 1 be insufficiem! for understanding of the global symmetsy (Bardcle, 1977}, Hence, we ean ask whether MAP attachment site pattern formation is comtolled by a globul in these structures jenply diffe