IIScEver wonder about the world inside a living cell? How the different organelles coexist and communicate with each other? Advanced microscopy has contributed immensely in our understanding of cell structure, yet gathering information on processes like cellular communication in real-time has always been a challenge. Who would have thought that a serendipitous cab ride shared by a physicist and a biologist would lead to a solution?
Ambarish Ghosh (The Physicist) from the Centre for Nano Science and Engineering (CeNSE), Indian Institute of Science (IISc), Bangalore, and Deepak Saini (The Biologist) from the Department of Molecular Reproduction, Development and Genetics, also from IISc, Bangalore, along with their multi-disciplinary research group, created magnetic nanomotors that can be used for exploring a cell from the inside.
Nanomotors are extremely small devices that translate electrical, ultrasonic or chemical energy to mechanical energy. They are usually 200-400 nm in size, where 1 nanometer(nm) is equal to one billionth of a meter. They can be used to navigate different types of fluid environments and are often used in physics and nanoengineering -related applications. But recently, researchers have begun exploring the ways in which nanomotors could be fabricated, designed and moved in biological fluids like blood, urine, saliva, mucous etc.
So far, existing nanomotor systems suffered from a few major disadvantages, limiting their use for biomedical applications. Firstly, nanomotors could be manipulated only in cells in suspension, preventing the use of adherent cell culture model systems, which constitute the majority of cells used for biomedical research. Secondly, these systems would often result in physical damage to the cells. And finally, there was no efficient way to manoeuvre these nanomotors precisely in the complex biological environment inside a cell.
Ghosh and Saini’s group managed to overcome all of these problems by combining the principles of biology with the tools of physics. Ghosh, who had already been experimenting with designing and fabricating efficient nanomotors that can move in biological fluids, came up with helical magnetic nanomotors. His ultimate goal was to study his nanomotors, or “bio-swimmers”, as he calls them, in a living system. But biological systems were unfamiliar to him and this felt like an insurmountable challenge.
Along came Saini, with whom Ghosh shared a cab ride which lasted one-and-a-half-hours and led both scientists to end up discussing their respective research interests. Saini’s lab works on signalling in ageing, inflammation and infection, and he had a few ideas of his own about how one could experiment with nanomotors inside living cells.Researchers who worked on the nanomotor project (Bottom, left to right: Malay Pal, Anumeha Singh, Neha Somalwar ;Top , left to right: Sandeep M Eswarappa, Ambarish Ghosh, Deepak Saini, Ramray Bhat
A cell contains many complex structures and compartments (called organelles) suspended in a viscous medium called cytoplasm, whose exact physical properties are not properly understood. The challenge was to manoeuvre Ghosh’s bio-swimmers in an overcrowded, but essentially blind territory. The nanomotors manufactured in Ghosh’s lab were fabricated with iron and therefore responded to magnetic fields. Being helical, they could be propelled forward or backward in a viscous medium more efficiently than other geometrical shapes (akin to a screw being able to course through wood, compared to a nail or any other shape object).
The researchers could control the movement of the nanomotors inside the complex milieu of the cell by alternating the strength and polarity of the magnetic field. And whenever a nanomotor encountered a physical hurdle that made it stop, the system was designed to retract it and change its course by a few degrees, repeating this step if necessary till the nanomotor could freely move. This circumvented the crowding issue. This strategy is quite similar to how space-probes are designed to move on an unknown planet surface.
Saini and his group designed a system for safely introducing the nanomotors inside adherent cells. They found that these nanomotors are biologically compatible, i.e. they do not cause any cell death upon entering or moving around in cells. Thus, together, the researchers created an efficient and safe system for delivery of bio-swimmers inside the cells, with complete and accurate manoeuvrability in the cells.
The potential applications of nanomotors in biophysical research are many. According to Ghosh, they can be used as a probe for measuring the local environment in the cell, or to create a mechanical map of the cell, which no technique has been able to do so far.
Roop Mallik, Tata Institute of Fundamental Research (TIFR), Mumbai, who was not associated with this research, appreciated the collaborative effort to develop these magnetic nanomotors. “This is something to look forward to,” he said, adding that “The real challenge is how to incorporate and release a drug from these structures in targeted manner? How to target them to specific cell-types in an animal? I am sure there will be exciting advances in this direction from the present authors and others in future.”Helical nanomotors : Exploring the cell from within (Image: Divya Sriram)
The team is now experimenting with mouse models to see how they can introduce these nanomotors into tissues in live animals. One of the next steps is designing a whole-body imaging system to track these nanomotors inside the mice. Saini added that once they figure out how to introduce nanomotors effectively in live organisms, they could be easily tagged with antibodies specific to certain cell types, for e.g., cancer cells, for targeted drug delivery. Ghosh and Saini’s groups are currently collaborating with Kidwai Memorial Institute of Oncology, Bangalore (KMIO) to explore the use of these magnetic nanomotors for advanced drug delivery into cancer cells derived from patient samples.
Just as a space probe or rover explores and gathers information of the planet, while being guided remotely through Earth, we can think of the magnetic Nanomotors as mini-satellites or nano-voyagers that will aid in visualisation, studying the local environment and delivering specific “payloads” (like, drugs) to a cell, being manoeuvred remotely through magnetic fields. In the meanwhile, Saini and Ghosh continue to hold regular coffee meetings to discuss everything from precise drug delivery to other biomedical applications.
Indian researchers are slowly catching the interdisciplinary wave to solve scientific questions that cannot be addressed by sticking to one discipline alone. If we are to compete at a global platform in scientific research and innovations, we must open our mindset for alternate ways of addressing a question at hand. For young researchers to develop this inter-disciplinary culture, Ghosh and Saini both strongly recommend students to talk to their peers from other fields, taking time to explain their research and also try to understand the different points-of-view provided by experts of other fields. Many a times, a lot can happen over coffee, if once in a while you just care (or dare) to venture out of your department canteen to the next one!
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This is a companion discussion topic for the original entry at https://indiabioscience.org/columns/general-science/magnetic-nano-motors-nano-voyagers-inside-cells