JP2009183159A - Biological substance communication method and biological condition formation method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biological substance communication method for efficiently carrying out decoding even if the structure of loaded molecule is unclear. <P>SOLUTION: A transfer pathway 144 of a biomolecular motor 12 is formed between living cell substances 140 and 142. The biological substance communication method includes the steps of: providing a stimulation 150 to the first living cell substance 140; combining a signal transfer protein 158 formed by a signal transfer network 154 in the living cell substance 140 caused by the stimulation 150 with the biomolecular motor 12 in the living cell substance 140; detecting a signal transfer protein 182 formed by a signal transfer network 180 in the living cell substance 142 caused by the protein 158 by the transfer of the biomolecular motor 12 through the transfer pathway 144 and arrival at the living cell substance 142; and decoding the stimulation 150 provided to the living cell substance 140 by a code book based on the detected protein 182. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a communication method using a biological material, and more particularly to a communication method using a motor protein.

  With the development of nanobiotechnology, research to utilize nanobiotechnology in the so-called ubiquitous society has become active. For nanobiotechnology, conventional communication technology cannot be applied as it is, and it is necessary to use substances present in cells.

  Patent Document 1 utilizes the fact that a carrier molecule such as a microtubule or an actin filament that interacts with a motor protein can be slid along the channel on a substrate channel on which kinesin, which is a motor protein, is immobilized. In addition, a technique is disclosed in which a load molecule is autonomously separated from a carrier molecule at a desired location after the load molecule is loaded on a carrier molecule and transported.

Patent Document 1 further suggests that a molecular communication system is realized by previously encoding information to be transmitted into a package molecule and decoding the encoded information on the receiving side for loading and unloading the package molecule.
JP 2007-1111004 (paragraphs 7, 8, and 49)

  However, in the technique disclosed in Patent Document 1, single-stranded nucleotides are bound to both a cargo molecule and a carrier molecule, and the cargo molecule is transferred to a carrier by a double-stranded nucleotide generation reaction that occurs between the single-stranded nucleotides. Load on the molecule. In order to cause this reaction, the load molecule must be in the vicinity of the carrier molecule, and there is a problem that the load molecule cannot be efficiently conveyed to the receiving side. On the receiving side, it is necessary to extract the load molecules after the load molecules are removed from the carrier molecules. Further, even after the parcel molecule is extracted, in order to decode the information encoded in the parcel molecule, it is necessary to examine the structure of the parcel molecule, and there is a problem that decoding cannot be performed efficiently.

  In addition, it is preferable that the state of the biological substance itself can be set to a desired state using not only information but also luggage molecules. However, conventionally, such a method has not been proposed.

  Therefore, an object of the present invention is to provide a biological material communication method capable of performing decoding efficiently even if the structure of the luggage molecule is unknown.

  Another object of the present invention is to provide a method for generating a biological state in which the state of a biological substance can be set to a desired state by using luggage molecules.

  The method according to the first aspect of the present invention is a biological material communication method for transmitting information from a first biological cell material to a second biological cell material. Between the first biological cell material and the second biological cell material, a movement path of a biomolecular motor existing in the first biological cell material is formed. In this method, a stimulus applying step for giving any one of a predetermined group of chemical substances to a first biological cell substance, and a chemical substance given to the first biological cell substance in the stimulus applying step A binding step of binding a first signaling protein, which is a target factor generated by a signaling network in the first biological cell material, with a biomolecular motor in the first biological cell material; The biomolecular motor coupled to the first signaling protein moves along the movement path to reach the second biological cell material, thereby causing a signal in the second biological cell material due to the first signaling protein. A detecting step for detecting a second signaling protein produced by the transmission network, and detecting in the detecting step. Based on the second signaling protein was, and a decoding step of decoding the stimulus provided by the previously prepared codebook to the first biological cell material.

  When a stimulus is applied to the first biological cell substance, a first signal transduction protein as a target factor is generated by a signal transduction network resulting from the stimulus. This protein is combined with a biomolecular motor and transported to a second biological cell material. When this protein reaches the second biological cell material, a second signal transducing protein is generated by the signal transduction network in the second biological cell material due to the protein. By detecting this signal transduction protein, determining what it is, and comparing it with the codebook, the stimulus applied to the first biological cell material is revealed. That is, on the second biological cell material side, it is possible to know what the stimulus given to the first biological cell material is. The stimulus given to the first biological cell material can be considered as encoding information to be transmitted. Eventually, the information transmitted from the first biological cell material on the second biological cell material side. Can be decrypted.

  Preferably, according to the information sequence to be transmitted, the method repeatedly performs the stimulus applying step, the combining step, the detecting step, and the decoding step while changing the stimulus applied to the first biological cell substance in the stimulus applying step. Thus, the method further includes the step of transmitting the information sequence to be transmitted to the second biological cell material.

  By repeating the above-described steps while changing the stimulus applied to the first biological cell material according to the information sequence to be transmitted, the second biological cell material is converted into the sequence of the signal transducing protein. Can be detected on the side. This sequence can be regarded as an encoded information sequence to be transmitted, and the transmitted information sequence can be decoded by comparing it with a codebook.

  The method according to the second aspect of the present invention is a biological state generation method for generating a desired state in the second biological cell material by applying a stimulus to the first biological cell material. Between the first biological cell material and the second biological cell material, a movement path of a biomolecular motor existing in the first biological cell material is formed. What signaling protein can be applied to the second biological cell material in any sequence in order to generate a desired state in the second biological cell material using the signaling network of the second biological cell material. It is assumed that it should be known in advance. According to the above-described sequence, the method specifies a sequence of a chemical substance to be provided in order to generate a signal transduction protein as a target factor in the first living cell substance, and follows the specified chemical substance sequence. A stimulus applying step for giving a chemical substance as a stimulus to the first biological cell substance, and a signal transduction network in the first biological cell substance by the sequence of the chemical substance given to the first biological cell substance in the stimulus applying step. A binding step in which a signal transduction protein that is a target factor that is sequentially generated is bound to a biomolecular motor in the first biological cell material, and a biomolecular motor that is bound in the binding step to a signal transduction protein that is a target factor in the binding step. The signal transduction protein that is the target factor via And a step of sequentially moving the second biological cellular materials.

  In order to generate a desired state in the second biological cell material, it is known in advance what signal transmission protein should be given to the second biological cell material in what sequence. Then, in the first biological cell material, if it is known what kind of stimulus should be given to generate a signal transduction protein as a target factor of the signal transduction network, the stimulus is converted into the first biological cell material in a specific sequence. By giving to, the signal transduction protein which should be given to a 2nd biological cell material in the 1st biological cell material can be produced | generated in the sequence which produces | generates a desired state. If these signaling proteins are sequentially transported into the second biological cell material by a biomolecular motor, the second biological cell material is given a signaling protein according to the sequence necessary to produce the desired state. Therefore, a desired state can be generated in the second living cell material.

  For example, the state of the second biological cell material can be changed so as to kill a specific recent item in the second biological cell material or destroy the specific material.

  Embodiments of the present invention will be described below. In the following description, the same parts or the same types of molecules are basically denoted by the same reference numerals. Their names, configurations, and functions are also the same. Therefore, detailed description thereof will not be repeated.

  Along with the development of nanobiotechnology, a protein substance called biomolecular motor has attracted attention. A biomolecular motor is a protein that plays a role in transporting chemical substances in a living body, and dynein, myosin, kinesin, and the like are known. These biomolecular motors are known to operate with ATP (adenosine triphosphate) or the like as an energy source and have extremely high energy efficiency.

  FIG. 1 is a diagram for explaining the operation of myosin molecule 12 as an example of a biomolecular motor. Referring to FIG. 1, myosin molecule 12 is a protein having a molecular weight of about 500,000, a head that binds to microtubule 10, a tail to which luggage molecule 14 binds, and an elongated chest that connects the head and tail. The total length is about 160 nm. The myosin molecule 12 is also a catalyst for hydrolyzing ATP, and uses energy at the time of ATP decomposition as an operating energy source. In addition, although the decomposition rate of ATP is slow only with the myosin molecule 12 and the decomposition energy is wasted, the presence of a protein called actin in the microtubule 10 makes the decomposition rate of ATP very fast, and the myosin molecule 12 However, it is possible to efficiently use energy at the time of ATP decomposition. Actin also serves as a rail during the movement of the myosin molecule 12.

  In the present embodiment, the same principle as that of the technique described in Patent Document 1 is used in that information is transmitted using the transport of the load molecule by the myosin molecule 12, but the load molecule 14 on the transmission side is used. The principle of signal transmission described below is used for detection of the cargo molecules 14 on the creation and receiving side, and a series of information is conveyed as a whole by carrying various cargo molecules in time series. Therefore, it is different from the technique described in Patent Document 1.

  In the present embodiment, information is encoded by using protein molecules having properties suitable for carrying information as luggage molecules. Then, when the protein molecule is generated on the information transmitting side and when the protein molecule is detected on the receiving side, a chain reaction in a biological cell substance called signal transmission is used.

  Various phenomena that occur in biological cell materials are always triggered by the action of some substance molecules. For example, the function of a cell is differentiated by the expression of a specific gene, or a specific substance is produced in the body in response to stimulation of a cell receptor. In other words, a certain result occurs for some reason. Between this cause-and-effect relationship, there is an information transmission mechanism that connects the cause and the result. In the living body, such information is transmitted by chemical substances. Such transmission of information by a chemical substance in a living body is called signal transmission. That is, signal transduction refers to a network system of interrelationships between molecules that cause various life phenomena.

  There are various substances used for signal transduction, and the most well-known one is a protein called GTP (guanosine 5'-3 phosphate) ase. The GTPase has an inactive state bound to GDP (guanosine 5'-2 phosphate) and an activated state bound to GTP. GTPases are usually inactive. Upon receiving a specific stimulus, GTPase GDP replaces GTP. This changes the physical or molecular structure of the GTPase. As a result of this change, the position of a part of the GTPase changes or part of the GTPase dissociates to act on other molecules (called target factors).

  The target factor shows a similar reaction in response to this action, and further acts on a subsequent signal transduction factor. Such signal transmission is performed over a plurality of stages, and as a result, the final target substance is activated and exhibits a predetermined function.

  For signal transduction, not only the aforementioned GTPase is used, but also molecules that control phosphorylation / dephosphorylation of proteins such as kinases and phosphatases are important. Similarly, molecular oxidation / reduction is considered to play an important role. Various pathways using such various proteins are used for signal transduction. These proteins are called signaling proteins (hereinafter referred to as “SPK”).

  Among such pathways, it can be confirmed experimentally that there is some relationship between, for example, a change in the binding state of a certain GTPase and a certain kinase phosphatase. It is also possible to quantify the relationship.

  As is clear from the above description, GTPase has two states, an inactive state and an active state. For example, if these represent 0 and 1 of digital information, one GTPase is generated on the transmission side, conveyed to the reception side by a biomolecular motor, and if detected on the reception side, information of 0 or 1 Can be transmitted. Since there are a plurality of types of GTPases, it is possible to transmit more information in one transport by changing the types of GTPases.

  On the information transmission side, a biological cell material is prepared in the culture medium, and an external stimulus is generated to generate a specific GTPase in an active state or an inactive state as a final target factor. As a result, GTPase of the target factor is generated by the signal transduction network in the culture medium by signal transduction. The generated GTPase is transported by the myosin molecule 12 to the culture medium of the biological cell material on the receiving side. The GTPase taken down from the myosin molecule 12 on the receiving side becomes a new stimulus, and various reactions are caused by the signal transduction network in the receiving side. By detecting a substance that can be easily detected from the outside among the substances generated by these reactions, the receiving side can know what is the causative substance of the substance, that is, the transmitted GTPase, The transmitted information can be decoded. By repeating this, information of a desired bit can be transmitted by the biomolecular motor in the form of GTPase.

  Signal transduction is a reaction that causes a change in the binding state of GTPase described above (this reaction is hereinafter referred to as “GTPase reaction”), a reaction that causes phosphorylation / dephosphorylation of SPK (hereinafter this reaction is referred to as “SPK reaction”). And a reaction that causes oxidation / reduction of these proteins (this reaction is hereinafter referred to as “oxidation / reduction reaction”).

  FIG. 2 schematically shows the GTPase reaction, SPK reaction, and oxidation / reduction reaction described above. Referring to FIG. 2A, in GTPase reaction 20, GTPase changes state between inactive GTPase 30 bound to GDP32 and active GTPase 40 bound to GTP42. . Giving GEF (guanine nucleotide exchange factor) 36 to inactive GTPase 30 replaces GDP32 that was bound to inactive GTPase 30 with GTP34, and active GTPase 40 bound to GTP42 can get. At this time, GDP 38 is dissociated.

  There is also a reaction that inactivates GTPase because it is inconvenient if GTPase remains activated. GTPase itself has the property of inactivating itself. However, basically, as shown in FIG. 2 (A), by giving GAP (GTPase activating protein) 46 to the activated GTPase 40, GTP42 bound to GTPase 40 is replaced with GDP44. Is done. GTP42 dissociates from GTPase 40 to become GTP48.

  In this way, the inactive GTPase 30 is activated in response to an external stimulus, thereby activating the target factor downstream of the signal transduction pathway. In response to the disappearance of the stimulus, the active GTPase 40 is activated. Return to the original state by inactivation. Thus, the reaction related to GTPase consists of a set of reactions of activation / inactivation. This property is important for realizing a signal transduction mechanism. In other types of reactions such as SPK reactions and protein oxidation / reduction reactions described below, a part of the signal transduction pathway is constituted by a set of reactions in the forward and reverse directions.

  The mechanism of the SPK reaction 22 relating to SPK60, which is another important factor responsible for signal transduction, is shown in FIG. Referring to FIG. 2 (B), SPK60 reacted with phosphorus (P) supplied from ATP (adenosine 5′-3 phosphate) 62 in the presence of specific kinase 64 and bound to phosphorus atom 70. SPK68. At this time, ATP 62 supplied with phosphorus loses phosphorus and becomes ADP (adenosine 5'-2 phosphate) 66.

  The reverse reaction is as follows. That is, the SPK 68 bonded to the phosphorus atom 70 breaks the bond with the phosphorus atom 70 in the presence of the phosphatase 74 and the ADP 72, and returns to the SPK 60. ADP72 binds to the phosphorus atom supplied from SPK68 to become ATP76.

  FIG. 2C shows a mechanism of a general oxidation / reduction reaction 24. Referring to FIG. 2 (C), protein 90 reacts with oxygen atom 92 obtained from any source molecule by oxidation action 94 to become protein 96 bound to oxygen atom 98. Due to the reducing action 100 on the protein 96 bonded to the oxygen atom 98, the oxygen atom 102 is dissociated from the protein 96 bonded to the oxygen atom 98, and the original protein 90 is obtained.

  These three types of reactions are considered to be the most important in signal transduction.

  FIG. 3 is a diagram for explaining the concept of signal transmission. Referring to FIG. 3, the signal transduction network is activated when a stimulus 110 (a specific chemical substance or the like) is given to a biological cell substance. By this stimulation, a plurality of inactive signal transduction proteins 112 are activated to generate an activated signal transduction protein 114. The activation signaling protein 114 further activates a plurality of inactive signaling proteins 116 to generate an activation signaling protein 118. Similarly, the activation signal transduction protein 118 activates the inactive signal transduction protein 120 to produce the activation signal transduction protein 122. Similarly, a number of reactions proceed in parallel through the signaling network, and the target factor is activated.

  FIG. 4 shows an information transmission method according to the present embodiment. Referring to FIG. 4, a transmission side culture medium 140 and a reception side culture medium 142 are prepared in advance. The transmitting side culture medium 140 and the receiving side culture medium 142 are filled with a biological cell material. A path 144 composed of actin and microtubules is formed between the two as a path for the movement of the myosin molecule 12. The path 144 can be formed, for example, by forming a pattern on a glass substrate and fixing actin and microtubules. The sending culture medium 140 and the receiving culture medium 142 contain the myosin molecule 12.

  As a result of the signal transmission, a stimulus 150 necessary to generate a desired type of active or inactive baggage molecule 158 is determined, and this stimulus 150 is given to the transmitting culture medium 140 when information is transmitted. Then, the SPK 152 that is directly activated by the stimulus 150 is activated, and a signal generated by the activation is transmitted through the signal transmission network 154 in the transmission side culture medium 140, and finally a desired luggage molecule 158 is generated, This binds to the tail of myosin molecule 12.

  The myosin molecule 12 to which the cargo molecule 158 is bound moves on the path 144 and reaches the receiving culture medium 142 as indicated by the arrow 162, where the cargo molecule 158 is lowered. In the receiving side culture medium 142, this luggage molecule 158 becomes a new stimulus, this signal is transmitted through the signal transmission network 180, and finally, a signal transmission protein molecule 182 to be detected is generated. Since the generated signal transduction protein is easy to detect, a signal corresponding to the stimulus 150 is transmitted from the transmission side culture medium 140 to the reception side culture medium 142 by detecting this as the external detection signal 184. I understand.

  FIG. 5 is a diagram for explaining that a series of information is transmitted from the transmission side culture medium 140 to the reception side culture medium 142 by repeatedly performing the information transmission shown in FIG. 4. Referring to FIG. 5 (A), by applying a stimulus 200 to the transmitting side culture medium 140, a load molecule 202 is generated through a transmission path similar to that shown in FIG. 4, and the myosin molecule 12 passes through the path 144. To the receiving side culture medium 142. In the reception side culture medium 142, a signal transmission protein to be detected is generated by a signal transmission network using the luggage molecule 202 as a new stimulus and detected as an external detection signal 204.

  Hereinafter, in FIG. 5B, the cargo molecule 212 generated by the stimulus 210 is transferred to the reception side culture medium 142 by the myosin molecule 12 and detected as the external detection signal 214 in the reception side culture medium 142. In FIG. 5C, the cargo molecule 222 generated by the stimulus 220 is transported to the reception side culture medium 142 by the myosin molecule 12 and detected as the external detection signal 224 in the reception side culture medium 142. In FIG. 5D, the load molecule 232 generated by the stimulus 230 is transported to the reception side culture medium 142 by the myosin molecule 12 and detected as the external detection signal 234.

  Assuming that the information A1, A2, A3, and A4 are represented by the stimuli 200, 210, 220, and 230, respectively, the information 250 transmitted from the transmission side culture medium 140 to the reception side culture medium 142 is “A1A2A3A4”. On the other hand, the information 252 represented by the signal detected on the receiving side culture medium 142 side is “B1B2B3B4”. The information “B1B2B3B4” detected on the reception side represents the information “A1A2A3A4” by preparing the correspondence between the stimulus on the transmission side and the detection signal on the reception side as a code book in advance. I understand.

  That is, desired information can be transmitted to the reception side culture medium 142 by sequentially giving a stimulus corresponding to the information to be transmitted to the transmission side culture medium 140.

  In addition, according to the method according to the present embodiment, it is not only possible to simply transmit information from the transmission side culture medium 140 to the reception side culture medium 142. It is only the desired signal transduction protein that is produced in the receiving side culture medium 142. If these signal transduction proteins are given to living cells according to a certain sequence, if it is found that the inside of the living cells can be brought into a specific state, the signal transducing protein is generated in the receiving culture medium 142 by the sequence. If a stimulus is given to the transmission side culture medium 140 in such a sequence, the biological cell substance in the reception side culture medium 142 can be brought into the specific state described above. That is, by this method, there is a possibility that a state similar to that when a specific medicine is delivered into a living body can be generated.

  As described above, according to the present embodiment, the information to be transmitted is encoded by giving a stimulus to the living cell substance in a sequence according to the information to be transmitted to the reception side. A desired signal transduction protein can be produced in the biological cell material. By detecting the signaling protein, the transmitted information can be decoded.

  The embodiment disclosed herein is merely an example, and the present invention is not limited to the above-described embodiment. The scope of the present invention is indicated by each claim in the claims after taking into account the description of the detailed description of the invention, and all modifications within the meaning and scope equivalent to the wording described therein are intended. Including.

It is a figure explaining operation | movement of the myosin molecule | numerator 12 which is an example of a biomolecule motor. It is a figure which shows the outline of GTPase reaction, SPK reaction, and oxidation-reduction reaction. FIG. 3 is a diagram for explaining the concept of signal transmission. It is a figure which shows the information transmission method which concerns on one embodiment of this invention. FIG. 5 is a diagram for explaining that a series of information is transmitted from the transmission side culture medium 140 to the reception side culture medium 142 by repeatedly performing the information transmission shown in FIG. 4.

Explanation of symbols

10 Microtubule 12 Myosin molecule 14 Luggage molecule 110 Stimulus 112, 114, 116, 118, 120, 122, 152, 158, 182 Signaling protein 140 Transmitter culture medium 142 Receiver culture medium 150, 200, 210, 220, 230 Stimulus 154 , 180 Signal transmission network 204, 214, 224, 234 External detection signal

Claims (3)

A biological material communication method for transmitting information from a first biological cell material to a second biological cell material,
Between the first biological cell material and the second biological cell material, a movement path of a biomolecular motor existing in the first biological cell material is formed,
Applying a stimulus to the first biological cell material to give any one of a predetermined group of chemical substances;
A first signal transduction protein that is a target factor generated by a signal transduction network in the first living cell material due to a chemical substance given to the first living cell material in the stimulus applying step; A binding step for binding to a biomolecular motor in the first biological cell material;
Due to the first signal transduction protein, the biomolecular motor coupled with the first signal transduction protein in the binding step moves through the movement path and reaches the second biological cell substance. Detecting a second signaling protein produced by a signaling network in the second biological cell material;
A communication method using a biological material, comprising: a decoding step of decoding the stimulus given to the first biological cell material by a codebook prepared in advance based on the second signal transduction protein detected in the detecting step . By repeating the stimulus applying step, the combining step, the detecting step, and the decoding step while changing the stimulus given to the first biological cell material in the stimulus applying step according to the information sequence to be transmitted. The communication method using a biological material according to claim 1, further comprising a step of transmitting the information string to be transmitted to the second biological cell material. A biological state generation method for generating a desired state in a second biological cell material by applying a stimulus to the first biological cell material,
Between the first biological cell material and the second biological cell material, a movement path of a biomolecular motor existing in the first biological cell material is formed,
What signal transduction protein is used in the second biological cell material in order to generate the desired state in the second biological cell material using the signaling network of the second biological cell material. It is known in advance whether it should be given in a simple sequence,
The method
In response to the sequence, identifying a sequence of chemicals to be provided in order to generate the signaling protein as a target factor in the first biological cell material;
Applying a stimulus to the first biological cell substance as a stimulus in accordance with the identified sequence of chemical substance;
A signaling protein that is a target factor that is sequentially generated by a signaling network in the first biological cell material according to the sequence of the chemical substance applied to the first biological cell material in the stimulus applying step, A binding step for binding to a biomolecular motor in biological cell material;
Sequentially transferring the signal transduction protein as the target factor to a second biological cell substance via the migration path by the biomolecular motor coupled with the signal transduction protein as the target factor in the binding step. A biological state generation method.

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