06 May 2013

Cyborgs inside us?

The cells modified by scientists will become a formidable force in the fight against dangerous diseases

Firyuza Yanchilina, the newspaper "Search" No. 18-2013

The winners of RFBR competitions for leading youth groups often admit that they did not really believe that their project would be appreciated. But the prospects of research and the potential of their authors do not escape the attention of experienced experts of the foundation. These qualities are fully possessed by the work that we are talking about today...

What scientists don't do with cells! The properties they give to "living bricks" will help, in particular, to develop unique biotechnologies for the treatment of serious diseases.

In the Laboratory of Bionanotechnology and Biomaterials of Kazan (Volga Region) Federal University (KFU), under the guidance of Doctor of Biological Sciences Associate Professor Ravil Fakhrullin, magnetic cyborg cells are created using nanoparticles. The study was supported by a grant from the Russian Foundation for Basic Research. The scientist told the correspondent of "Search" about what "cyborg cells" are and how it was possible to get to such a topic with a fantastic bias.

– Our laboratory has been working on magnetically modified cells since 2008, - says Ravil Faridovich. – In the English literature there is a term “cell surface engineering” – cell surface engineering. This scientific direction deals with changing the surface of living cells. This is done with the help of functional nanomaterials: nanoparticles, polymer films, nanotubes and various combinations of them, which makes it possible to strengthen or modify the useful properties of cells, as well as to assemble multicellular structures from them. Just as different structures are made up of cubes. We can attach them to various surfaces, larger particles, move them in space or supply them with nutrients from nanocontainers.

We call such nanomodified "bricks" "cyborg cells" by analogy with the heroes of science fiction films. Unlike movie cyborgs (artificial mechanisms, but with living skin), ours are living organisms with artificial coating. The most significant of our previous studies were aimed at creating methods of magnetic modification ("functionalization") of microbial cells and artificial multicellular systems.

We used magnetic microbial cells to develop biosensor systems, for example, toxicity assessment. To do this, special nanoparticles were attached to the cell walls, after which the cells became magnetically susceptible, that is, they were attracted to a permanent magnet. And applying a multilayer polymer "fur coat" to the yeast surface allowed us to obtain multicellular "cytosomes" – microparticles consisting of living cells and outwardly resembling primitive colonial organisms. Even then, we conceived the idea of using magnetic modification methods on human cells, which we tested on microbes. The use of a magnetic field opens up the possibility of creating prototypes of biological tissues.

Tissue engineering is now one of the most promising areas in biomedicine. The results of research in this area will make it possible to obtain new artificial tissues and even organs that can be transplanted to patients. Over time, transplantologists will be able to replace donor materials with them. All problems with biocompatibility will be removed. Today, these technologies are mainly at the stage of laboratory testing, but in the future they will occupy a worthy place in medical practice.

– What are magnetically modified cells and how are they "manufactured"?

– Our research is aimed at obtaining, as well as determining the characteristics of magnetic "cyborg cells", that is, such human cells, to the surface of which nanoparticles with special properties are attached. This modification of cells has been known for a long time, and its main advantage is that cells can be "controlled at a distance" using a magnetic field. This method is very convenient: you can use magnets to lay cells in multilayer structures.

Many research groups have been using methods for quite a long time in which cells are provided with magnetic tags – for this, magnetic nanoparticles are injected into their "insides" in one way or another. It takes a lot of time, and most importantly, tiny particles inside cells can significantly affect their viability. Today it is still impossible to speak with certainty about the possible long-term effects caused by their introduction into living structures.

The novelty of our approach is that we attach nanoparticles to the surface of cell membranes, they practically do not penetrate into cells. In this way, we minimize the possibility of negative effects of nanomaterials on enzymes and the genetic apparatus. As a result, magnetic "cyborg cells" are capable of growth and division as efficiently as intact (that is, the original, non-magnetic) ones. In addition, the magnetization method we use requires significantly less time to tag cells: nanoparticles attach to them under physiological conditions in 10-15 minutes, whereas alternative methods require a longer period (up to 72 hours).

Unlike microbes, mammalian cells are not protected by a massive cell wall, which significantly complicates the process of modifying their surface. Nanoparticles must have colloidal stability in physiological environments. Within the framework of the project awarded by the RFBR grant (which supports the work carried out by leading youth collectives), we synthesize such particles, stabilizing them with biocompatible polymers, and they are able to attach to cells. As a result, such cells coated with nanoparticles behave like microscopic magnets, they can be concentrated and held in space, for example, with the help of a simple permanent magnet.

Today we use such living structures with additional properties to create artificial multilayer cell clusters – tissue prototypes. For example, we can layer cells on top of each other, which allows us to recreate the structure of natural material to some extent. In addition, the methods that we are developing can be used in cases where it is necessary to ensure the targeted delivery of one type of cell to a specific human organ, where it is necessary to create a high concentration of them.

– In order to carry out such complex research, it seems to me that a large group of specialists and good equipment are needed. Do you have all this?

– Our team cannot be called large: including me, there are three researchers, a graduate student, a master's student and two students. But we try to work no worse than numerous groups. My employees are specialists in the field of cell biology, physico–chemical research methods, microscopy. Each of them is involved in a project, the implementation of which involves the synthesis of nanoparticles, the study of their characteristics and toxicity, experiments on magnetic modification of cells.

We work at Kazan University, one of the oldest universities in the country. In recent years, KFU has significantly updated the park of laboratory equipment, now we have the opportunity to use many modern research methods. The most valuable thing in our team is the relationship between people based on mutual understanding, respect, support. Everyone is engaged in the work that is interesting to him. As a leader, I determine the general direction of research, but any of the team members independently solves many current issues, suggests new topics. Research on the nanomodification of cells requires high-quality training of an employee, he must possess modern research methods. In addition, you need to be very careful and patient: working with small objects is impossible without a reverent attitude to them. In general, the secret of our success is people. We have publications in prestigious magazines, wins in various specialized competitions. We often exchange information with colleagues, including foreign ones, and a modern scientist cannot do without such an exchange of experience and knowledge. And, of course, we work closely with other research groups of our university.

– Have you already done some of the work?

– The first stage of the project is almost completed. Nanoparticles were synthesized and their characteristics were determined. Magnetic modification of isolated human cells was performed. Model cells magnetized with nanoparticles were selected. Experimental conditions for their optimal magnetization have been determined. This is routine, but necessary work: it is necessary to determine the concentrations of reagents, incubation time, and much more. In addition, studies were conducted to assess the toxicity of magnetic nanoparticles in relation to cells and found that magnetic modification does not have a negative impact on their vital functions. The results of their research have already been sent for publication in one of the relevant international journals.

– What are you planning to do with the grant funds?

– The RFBR grant gave us the opportunity to conduct research using mammalian cell cultures. Tests in the field of cell biology are expensive. Consumables, reagents, nutrient media for maintaining human cell cultures are much more expensive than similar materials for microbial cells. With the funds received, we will also purchase equipment to study the effect of nanoparticles on cell viability. In short, the foundation has provided substantial support to our research.

The second stage of the project will be devoted to the creation of multi-layered multicellular clusters that mimic human tissues. Of particular interest to us is the creation of materials that imitate the "lace" of a light person. We plan to develop other models as well.

– What are the prospects for using magnetically modified cells?

– The main task of the current project is to create a methodology for the magnetization of human cells. It is important that it can be quickly and easily applied in clinics. We hope that the results of our research will be useful to other groups of scientists working in this direction. The methods we have proposed are universal, they can be used for any type of cells. This will allow the use of magnetic "cyborgs" in the construction of organs and tissues, targeted delivery of "therapeutic" cells, as well as in magnetic resonance imaging.

We will continue research on the development of new methods of cell surface engineering, including magnetic modification of cells. We are interested in designing multicellular structures with unusual morphology, as well as in creating nanoparticles that, in addition to the magnetic function, would have other useful properties, such as protective ones.

Portal "Eternal youth" http://vechnayamolodost.ru06.05.2013

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