Danko Georgiev 2

Further papers relative to Danko Georgiev

1.) Dissipationless waves for information transfer in neurobiology - Danko Georgiev - Informatica, 30 (2006 - Discussion of solitons and information processing in microtubules.

2.) Neuronic system inside neurons: molecular biology and biophysics of neuronal microtubules - Danko Georgiev - Clearest version of Georgiev's theory of quantum information processing in microtubules.

3.) Neurologins and neurexins - Thomas Sudhof - Relates to ideas on coherence between neurons

4.) Solving the binding problem: cellular adhesive molecules and their control of the cortical quantum entangled network - Danko Georgiev - Proposal for quantum coherence extending between neurons.

5.) Coherence in stable microtubules - Danko Georgiev - Computation in microtubules driven by electric field and elastic energy in microtubules

6.) A non-linear model of ionic wave propagation along microtubules - Sataric, M., Tuszynski, J. et al - European Biophysical Journal, (2009), 38: pp. 637-47, DOI 10.1007

7.) Tubulin-Bound GTP: Towards a revision of microtubule based quantum models of the mind - Danko Georgiev

1.)

Dissipationeless waves for information transfer in neurobiology

Danko Georgiev & James Glazebrook, Kanazawa University & Eastern Illinois University

Informatica, 30 (2006) pp. 221-32

Solitons or solitary wave quanta can retain their form and velocity when undergoing collisions. Pairs of soliton waves are seen to pass through one another. The authors refer to the work of Davydov on solitons (1&2.), which is seen as a basis for proposing dissipationless energy transfer in organic matter, and in particular influences on dendritic and axonal microtubules, information processing within neurons and generation of synapses.

The cytoskeleton dynamically regulates neurons, and is formed by self-assembling protein networks. Microtubules are the main constituents of this network, and interact with other cytoskeletal structures such as actin filaments, microtubule associated proteins (MAPs), and various scaffold proteins. Microtubules are formed out of sub-units of tubulin protein. A study by (3. Sackett, 1995) revealed that each tubulin has a 4-5 nanometre 'tail' that is extremely sensitive to environmental conditions and local electrical fields, and as a result produces a large number of different conformations (4. Georgiev, 2003a). It is emphasised that microtubules are not passive tracts for molecules to be moved along, and relative to this, it has been shown that the tubulin tails can modulate the function of the motor protein, kinesin (5. Skiniotis et al, 2004). Tubulin tails can also attach to MAPs, protein kinases and phosphatises, while microtubule anchored enzymes such as phosphatases and kinases are tuned by microtubules. These processes may involve soliton assisted tunnelling (6. Sutcliffe & Scrutton, 2000).

The cytoskeleton constitutes a protein surface, to which water molecules attach, and this allows the water to become ordered. Ordered water molecules interact via hydrogen bonds. On the basis of another study (7. Jibu et al, 1997), it is suggested that the ordering of water on the microtubule surface creates long-wave correlations of electric dipoles or dipole wave quanta (DWQ). It is suggested that the water molecules and the tubulin tails react with the local electromagnetic field to allow solitons to travel along the microtubules. Coherence time is estimated at 10-15 picoseconds, to be compatible with the action of protein.

The authors further suggest the possibility that the complex of the presynaptic scaffold protein network links mictotubules to synaptic vesicles. This is suggested to involve the protein synaptotagmin, and would connect microtubules directly to the firing of synapses.

References:-
1.) Davydov, A. (1982) - Biology and Quantum Mechanics - Pergamon Press
2.) Davydov, A. (1991) - Solitons in Molecular Systems - Kluwer, Dordrecht
3.) Sackett, D. (1995) - Structure and function in the tubulin dimer and the acid carboxyl terminus - Subcellular Biochemistry Proteins, 24, pp. 255-302
4.) Georgiev, D. (2003a) - Electronic and magnetic fields inside neurons - cogprints.org/3190/
5.) Skiniotis, G. et al (2004) - Modulation of kinesin binding by the C-termini of tubulin - The EMBO Journal, 23, pp. 989-9
6.) Sutcliffe, M. & Scrutton, N. (2000) - Enzyme catalysis - Trends in biochemical science, 25, (2000), pp. 405-8
7.) Jibu, M. et al (1997) - Evanescent photon and cellular vision - Biosystems, 42, pp. 65-73

2.)

Neuronic system inside neurons: molecular biology and biophysics of neuronal microtubules

Danko Georgiev, Stelios Papaioanou, & James Glazebrook, Dept. of Anesthesiology, Varna, Medical University of Varna, Eastern Illinois University

Biomedical Reviews (2004), 15, pp. 67-75

'We dance round in a ring and suppose
but the secrets sits in the middle and knows' - Robert Frost

INTRODUCTION: This is possibly the clearest version of Georgiev's ideas on quantum information processing in microtubules that I have come across to date. Amino acid tails projecting 4-5 nanometres out from the surface of microtubules play a key role in the theory. The tubulin tails interact with the electric field, with water molecules, and with ions bound to the microtubular surface, to produce solitons (solitary quantum waves that, even in collisions with other waves, retain their shape and velocity). Collisions of these solitons act as logic gates, and the conformation of the tubulin tails controls microtubule associated proteins (MAPs) and motor proteins, which in turn constitute a computational output. It is also suggested that tubulin tails could regulate the output of neurotransmitters from synapses via presynaptic scaffold proteins. This would bring microtubules centre stage, within the conventional model of the brain's information processing. One advantage of this model is that it does not require the shielding from decoherence envisaged in the better known Hameroff theory, because the process suggested could occur within the normal time to decoherence in the brain.

The authors' detailed investigation of the interior structure of neurons is stated to indicate that microtubule networks inside neurons are suited to carrying out computation. Microtubules in neurons are more stable than in other body cells, and this makes them more suitable for information processing and signalling.

The authors discuss the better known ideas of Stuart Hameroff and his coworkers, as to how microtubules might process information. In Hameroff's version, the conformation of the tubulin is governed by electrons in hydrophobic pockets between the alpha and beta monomers of the tubulin dimer. Electrons in different pockets are suggested to be quantum entangled.

The authors argue against this particular model for information processing in microtubules. Hameroff's version assumes that the process derives its energy from the hydrolysis of GTP. However, the authors claim that this form of energy generation is impossible, once a stable microtubule has been assembled. Instead, they look for an alternative form of energy. On the basis of a mathematical model developed by the quantum consciousness researchers Jibui & Yasue, they claim to show that signals from the local electric field could govern the conformation of the so-called tubulin 'tails', which are amino acid carboxyl or C-terminals projecting 4-5 nanometres out from the surface of the microtubules. These projections are negatively charged, and the study suggests that they would attract positive ions, and thus form a Debye layer. They suggest that the projecting tubulin tails plus the hydration shells (water molecules orientated by ions) around the tails could make the microtubules very sensitive to their environment and particularly to the local electric field. It is suggested that the interaction between the tubulin tails and the local electric field could induce conformational waves in the tubulin tails. Tubulin tail interactions with MAPs, motor protiens and presynaptic scaffold proteins could allow the output of this computation.

Mathematical modelling suggests the feasibility of solitons formed by collective tubulin tail behaviour. The authors are interested in a particular type of soliton known as a 'breather', where internal oscillations create a more complicated structure than in other solitons. The shape and velocity of the soliton is not changed by collisions, but it can be shifted along the microtubule, and these collisions and shifts are suggested to act as logic gates for computation. The resulting conformation of the tubulin tails can become the output of computation, by determining the position of MAPs and motor proteins.

A study by Fujii & Koisumi (1.) showed that MAPs bind to tubulin C-terminals and the initial segment of the tubulin tail, and this makes it reasonable to assume that the tubulin tails are the main regulators of MAP binding. Another study (Skiniotis, 2) has shown that tubulin tails interact with the motor protien kinesin, and are involved in tethering motor protiens between active steps. Microtubules are involved in the transport of organelles that may form synaptic vesicles and membranes, and these objects may also contain neurotransmitters. Intracellular transport involves motor proteins, and the best studies of these are kinesin and dynien that use microtubular tracks, and are essential for transport within neurons. The authors claim that their studies change the view of microtubules from being passive tracks for transport, to being controllers of intracellular transport.

Synaptic control: It is further suggested that tubulin tail conformations can control the presynaptic scaffold proteins that organise synapses, and regulate the release of neurotransmitters. Studies (3. & 4.) showed that tubulin tails interacted directly with synaptotagmin-1. It is suggested that this protein could bind to microtubules, and prevent the depolymerisation that would otherwise occur as a result of Ca2+ ions in the presynaptic space. It is suggested that microtubules could be linked to synaptic vesicles by synaptotagmin or other scaffold proteins, and could thus regulate neurotransmitter release. The probability of an axon spike leading to the actual firing of a synapse ranges from 15-70%, so the relationship is far from one-to-one. This makes external regulation by microtubules feasible.

References:-
1.) Fujii, T. & Koizumi, Y. (1999) - Identification of the binding region of basic calponin on alpha and beta tubulins - Journal of Biochemistry (Tokyo), 125, pp. 869-75
2.) Skiniotis, G. et al (2004) - Modulation of kinesin binding by the C-termini of tubulin - EMBO Journal, 23, pp. 989-99
3.) Hirokawa, N. et al (1989) - The cytoskeletal architecture of the presynaptic terminal and the molecular structure of synapsin-1 - Journal of Cell Biology, 108, pp. 111-126
4.) Schmoranzser, J. & Simon, S. (2003) - Role of microtubules in fusion of post-Gologi vesicles to the plasma membrane - Molecular Biology Cell, 14, pp. 1558-1569

3.)

Neuroligins and neurexins

Thomas Sudhof, Stanford University

Nature, vol. 455, 16 October 2008, doi:10.1038

INTRODUCTION: Although it is not part of Sudhof's article, it has been separately suggested that the neurexin/neuroligin complex could allow quantum coherence that is proposed to arise around microtubules, and might also involve presynaptic scaffold proteins, to pass through the synaptic cleft to subsequent neurons, and thus presumably a whole neuronal assembly. This has been put forward as an alternative to Hameroff's suggestion that coherence is transmitted across a whole neuronal assembly via gap junctions.

Neurexins and neuroligins are cell-adhesion molecules that connect the presynaptic area of one neuron with the postsynaptic area of another, mediate signalling across the synaptic cleft, and specify syanptic functions. The complex is suggested to be important in the maturation of synapses, and in specifying the properties of particular circuits. Studies suggest that neurexin and neuroligin are not, however, essential for synaptic formation, but may be for subsequent maturation and function. Synapses have high plasticity, and changes in them can alter the relative contribution of synapses in a circuit. These changes probably depend on the action of the cell adhesion molecules, neurexin and neuroligin. These molecules probably bind to one another, and interact with proteins within the neurons. Current studies suggest that they mediate signalling between presynaptic and postsynaptic areas. Neurexins come in many isoforms, and it is suggested that these could code for different interactions at the synapses.

4.)

Solving the binding problem: cellular adhesive molecules and their control of the cortical quantum entangled network

Danko Georgiev, Medical University of Varna

Cogprints: 2 May 2003

INTRODUCTION: The author proposes a model by which quantum coherence arises in the cytoskeleton, is transmitted to the synapse, and from there to neighbouring neurons via the neurexin-neuroligin complex in the synaptic cleft. This is suggested to bring a large group of neurons into quantum entanglement, and to provide a solution for the binding problem.

The article proposes a possible process to support quantum entanglement between neurons, based on neurexin and neuroligin. This involves the 20-30 nanometre wide synaptic cleft, which is filled with electron-dense material. The presynaptic side has an active zone containing vesicles of neurotransmitters. Apart from signalling processes, there is also an adhesive junction at the synapse formed by neurexins and neuroligins. These are brain specific molecules, which bind to one another, and are part of a family of molecules known as CAMS, which are often present at synapses. The author claims growing evidence for the role of CAMs in modulating both short and long lasting plasticity. Receptors required for longer term potentiation (LTP) may be linked to the modulation of the cell adhesion proteins. Adhesion proteins could modulate glutamate receptors, possibly by altering the width of the synaptic cleft, and the size of the pre and post synaptic active zones, and also by altering glial cell processing around the edge of the synapse. Neurexin and neuroligin appear well suited to link pre and postsynaptic signalling mechanisms. The C-termini of neuroligins are inside the postsynaptic neuron and bind to the PDZ, which is thought to act as a nexus for receptors and signalling molecules on the postsynaptic side. The C-termini of the neurexins binds to CASK another PDZ containing protein on the presynaptic side.

The author relates these structures to the proposal that the cytoskeleton is important to the processing of incoming information in the brain, and that macroscopic quantum coherence arises in the cytoskeleton. Beyond this, he is looking for a means by which coherence passes from one neuron to another. He has rejected the Hameroff proposal that this happens via gap junctions between dendrites.

There is a thickening of the cell membrane on both sides of the synapse. The postsynaptic density (PSD) has been proposed to be a protein lattice that organises receptors, ion channels and signalling molecules. The proteins in the lattice contain PDZ domains involving PSD-95 that can bind to many types of synaptic proteins, including receptors for the main excitatory synapse. CASK, a presynaptic protein and PSD-95 stabilise the synapse by interacting with neurexin and neuroligin cell adhesion molecules, or by indirectly linking synaptic proteins to the cytoskeleton. CASK is tethered to the cytoskeleton by an actin binding protein. The author suggests that the neurexin-neuroligin cell adhesion complex could be connected indirectly to the cytoskeleton and mediate interneuronal quantum entanglement across the syanptic cleft. This is suggested to allow coherence across a large group of neurons, as a way of solving the binding problem.

5.)

Coherence in stable microtubules

Danko Georgiev, School of Medical Science, Kanazawa University

Neuroquantology, December 2009, vol. 7, 4, pp. 538-47

Stable microtubules comprise a large proportion of neurons, and are the main component of the cytoskeleton, which supports the extended dendritic arborisation and the axons of the neurons. Most neuron microtubules are stabilised by the cross-linking of microtubule associated proteins (MAPs), and the capping of the ends of proteins, both of which suppress frequent assembly and disassembly of the microtubules. This greater stability in neuron microtubules answers the often asked question, as to why non-brain microtubules are not seen as a basis of consciousness. But this does not prevent the non-consciousness of microtubules outside the brain being trundled out as an argument against quantum consciousness.

In dendrites, cross-linking is performed by MAP2 and in axons by MAP-tau. The author argues that the GDP and GTP molecules are not able to provide energy for computation within the microtubule, and energy from their processes is argued to go into the microtubule wall, as a result of the stretching of pre-existing bonds between the tubulin dimer subcomponents in the microtubule lattice. The microtubules are composed of 13 protofilaments. The tubulin subcomponents or dimers are connected by longitudinal bonds within the same protofilament and lateral bonds between dimers in different protofilaments. Here, chemical energy has been transduced into stored elastic energy. The author considers that this stored elastic energy might be important for the microtubular functioning within cells. He suggests that microtubular computation might be driven by interaction between the electric field inside neurons and the charged elastic brain microtubules.

Reference:

Caplow, M. et al - Free energy stored in the microtubule lattice - Journal of Cell Biology, 127, pp. 1918-24

6.)

A non-linear model of ionic wave propagation along microtubules

Sataric, M., Tuszynski, J. et al, University of Novi Sad and Cross Cancer Institute

European Biophysical Journal (2009) 38:637-47, DOI 10.1007

The cytoskeleton is a major component of all cells including neurons. It is comprised of actin filaments, intermediate filaments and microtubules, which are comprised of subcomponents of tubulin protein dimers, formed from an alpha and a beta monomer. These structures are organised into networks interconnected by proteins, with specific roles to play in the functioning of the cell. The microtubule is usually formed from 13 protofilaments. Each monomer of the tubulin dimer has a C-terminal helix, plus an amino acid sequence, projecting 4-5 nanometres out from the microtubule, and referred to as a tubulin tail (TT)

These TTs are involved in interaction with motor proteins and with the microtubule associated proteins (MAPs) that cross-link the microtubules. The alpha tubulin monomer TT is 19 amino acids long, with ten negatively charged residues. The TT on the beta monomer is nine amino acids longer. The detailed charge distribution on the tubulin surface results in a peak in electrostatic potential at every protofilament and a trough in the areas between them. The microtubule as a whole is suggested to be a 'cable' conducting 13 parallel ionic flows. The flow of ions along the microtubules is postulated to be mainly channelled through valleys in the electrical potential running parallel to each of the protofilaments. It is suggested that the TTs could significantly influence ionic current flow. The ions are suggested to flow at a radial distance from the surface of the microtubules.

The model proposed here is that microtubules with brush-like tubulin tails and surrounded by solvent ions in the cytosol act as electrical transmission lines. It is suggested that this model could provide some insight into a role for microtubules in information processing within neurons.

7.)

Tubulin-Bound GTP: Towards a revision of microtubule based quantum models of the mind P. Danko Georgiev, Kanazawa University, Neuroquantology, December 2009, 4, pp. 538-47 P. The author has developed a different proposal from Hameroff and some related researchers for the implementation of quantum consciousness in the brain; this would appear to include a Penrose-type quantum consciousness based on objective reduction of the wave function. P. The main body of this paper argues against the type of implementation proposed by Hameroff. The author considers that the release of sufficient GTP energy to form the basis of computation is not feasible within stable-state microtubules, since such a release of energy would lead to disassembly of the microtubule. I will not attempt to argue the rights and wrongs of the case as between Hameroff and Georgiev in respect of microtubule functioning. However, it does not appear that this paper should be taken as an argument against some form of Penrose-type quantum consciousness. At the end of the paper, the author expresses the hope that interaction between the electric field within the neuron and the 'charged elastic brain microtubules' might provide insight into information processing within neurons. His ideas in this respect are developed in greater detail in some of the other papers summarised in the Danko Georgiev section on this site.