Industrial engineer by training, Daniel García González (Leganés, 31 years old) began working in the aerospace area, studying aircraft materials. But biology crossed his path and he changed his professional destiny. Today, this investmentstigator of the Carlos III University (UC3M), National Youth Research Award 2023has one of the most promising careers in Spanish bioscience combining mechanics and biology.
Together with a multidisciplinary team, García González has developed a technological platform to reproduce in the laboratory what happens in the body when different pathologies occur, such as brain trauma, the progression of a tumor or the healing of a wound.
The technology, which uses smart and biocompatible materials that respond to magnetic stimuli, allows us to imitate in detail and simulate the changes that take place in these processes.
As if from a biological scenario in vitro In this case, the platform makes it possible to emulate the mechanical environment of the cells, the different conditions that can influence their behavior. García González explains it with a clarifying example. “Anyone who has done it knows that Running on asphalt is not the same as running on the sand on the beach.. The structural and mechanical environment affects the way we carry out an activity, it exerts an influence. The same thing happens with cells. The surrounding substrate, its rigidity, deformations or other mechanical signals also have a great effect. It is something that, for example, is clearly seen in a cancer process, where the environment of the tumor is key to determining how it grows or how it spreads,” he points out in his laboratory, while showing a sample of the smart cell substrate that the team has created.
An order on the computer sends a magnetic stimulus to the substrate, and the material begins to deform, as if we were touching it, pulling on it. “From the outside, in a non-invasive way, thanks to magnetic fields, we can impose certain mechanical states and see how the cells react,” explains the researcher. And in his words you can see the emotion of someone who feels that he has found a path with enormous potential to explore. The project has received funding from the European Research Council program (ERC Starting Grant and Proof of Concept), which supports scientific excellence.
«All this», he emphasizes, «has been possible thanks to a team with specialists from different disciplines that have allowed the combination of physical theories, computational models, synthesis of materials and developments of technological platforms, such as a 4D printer».
One of the scenarios that allows the platform to be emulated, called NeoMagis what happens in the brain when a blow to the head occurs.
In this type of trauma, “a very rapid, very abrupt and complex force is exerted on the brain that can have cognitive consequences,” explains García González. «The technology we have developed allows us reproduce all those mechanical effects in the laboratoryunderstand what happens to cells, how they deform, what happens in their structures and what the consequences are,” he adds.
In a recent article published in the magazine Advanced Materialsthe team has broken down what specifically happens to astrocytes, a type of brain cell, when faced with a simulated impact on the platform.
According to their analysis, the force of the blow generates a series of deformations that directly impact the structure of these cells, which becomes chaotic, and influences the mechanosensitive channels, an intracellular communication pathway that occurs through electrical signal exchanges. “The calcium signals that allow us to see how these cells are communicating show a first reaction in which the cells become altered, as if they wanted to scream and ask for help,” García explains in colloquial language. “But then we see that there comes a time when they become overwhelmed and that overexertion causes them to remain silent and not be able to communicate.” This alteration in communication, he continues, would explain the cognitive failures or memory loss that often result from a strong blow to the head.
«We are able to reproduce those deformation patterns in our smart substrate and even amplify them to 50%, above the levels that generate brain damage. And we can reproduce it while seeing what happens to the cells, something that was not possible until now,” highlights the scientist, who returned to Spain from Oxford with a talent attraction scholarship and now directs the Multifunctional Structures and Biomechanics at Carlos III University.
Reduce animal testing
The tool that the team has developed, García González points out with enthusiasm, opens the door to endless research and could make it possible to reduce animal testing.
It also highlights Clara Gomez Cruz, researcher of the unit and first signatory of the aforementioned work. «It is true that animal experimentation remains essential for scientific progress in biomedicine. However, I think it is important to highlight that the technology we have developed allows the study of the development of these diseases, reducing the need to resort to animal models for specific phases of research.”
In the future, if all goes well, the technology could even serve to modify the behavior of cells from the outsideusing magnetic fields, the researchers propose.
At first, the team thought the platform would be useful primarily for studies of neurological diseases, but as they have developed the tools, they have seen that the potential for applications is much broader and more varied. “The main challenge we face now is to standardize the technology and take it to different laboratories, so that we can transform basic or fundamental science research into solutions and return this work to society,” explains García González. To achieve this goal, the team has launched the spin-off 60Nd that seeks “to generate new methods to optimize the development of medical treatments, including biomechanical and mechanobiological considerations in them.”
The group of scientists has already started collaborations with different research groups interested in what the platform can offer. “For example, at the University of California in San Francisco they are interested in seeing how to generate heterogeneous patterns of these mechanical signals to differentiate stem cells,” says García González. «Another team in London wants to see how to use this technology to reproduce the mechanical forces that occur during embryonic development. On the other hand, with the Cajal Institute we are developing a project focused on Neurology and Johns Hopkins University, in the USA, wants to explore its use in breast cancer research».
During a stay at the Institut Pasteur in Paris, Clara Gómez Cruz will study the identification of the mechanical changes that occur in the glioblastoma, the most lethal brain cancer, and that allow tumor proliferation. “Finding these mechanisms is an important step to reach real solutions,” says García González, who emphasizes that although a priori it may seem that mechanics and biology are very separate, they really go hand in hand. “In fact, there is a very recent concept, mechanomedicine, which precisely focuses on finding mechanical mechanisms that can lead to different therapies or improve the diagnosis of different diseases.”
The researcher is convinced that it is at this confluence of disciplines, when the borders between different areas of knowledge intersect, where answers can be found to the scientific questions that remain unresolved. For this reason, the team includes mechanical engineers, biomedical engineers, physicists, biologists, neuroscientists… «It is very important to be aware of what you know and what you don’t, recognize it and look for people who complement your knowledge and allow you to the project continues to grow. “That’s the spirit we have, which is making things go quite well.”
From the Department of Mechanical Engineering at the Massachusetts Institute of Technology (MIT), Professor Ritu Raman, who also researches in the area of Mechanobiology independently of García González, points out that “the platform provides a significant advance that will benefit many researchers in this field”.
«Mechanobiology focuses on understanding how cells respond to forces in their environment. Professor García González’s technology allows both to simultaneously impose a series of forces on cells placed on a substrate and to measure how these cells change their rigidity in response to these forces,” he explains.
When he has an important experiment ahead, Daniel García González likes to meet with the team early to discuss the details and plan everything while they have breakfast. The best part, he says, is when he has to check if the hypotheses were correct, that moment eureka in which everything fits.
Ideas, however, do not always arrive in that community in the laboratory or in front of the computer. Many of the hypotheses that are later implemented in the laboratory have arisen in García González’s mind while he was playing sports, because the Madrid native, who is a lover of cinema and reading science fiction and has begun to learn to play the piano, comes out often to run. “It is very exciting to see that ideas that only a few years ago were purely theoretical and we did not know if they were going to work beyond paper are now a reality that can not only provide scientific knowledge but also have the potential to help in the clinic,” he concludes. .
The importance of uniting different disciplines
“The combination of experts from different disciplines, methodologies, different ways of thinking and posing the problem has greatly enriched the project, being key to achieving the final results,” says García González, who collaborated in the research that has just been published, for example with Armando del Río, a researcher specialized in the mechanisms by which cells are capable of transforming mechanical stimuli into biochemical signals. Del Río, who previously had his laboratory at Imperial College London and has recently moved to the Carlos III University, highlights that “one of the most interesting things about this work is that it answers many things but also opens up very broad questions.” For example, we have discovered that a molecule called PIEZO1, which is a very important cellular receptor in many biological processes, is involved in the functional responses that we have seen in astrocytes. This opens the door to asking many more questions. that we are already questioning both from the point of view of biology in general and specifically in neurology,” he points out.
For Arrate Muñoz, professor in the Department of Bioengineering and Aerospace Engineering at the Carlos III University and whose role has also been key in the recent research, the most innovative thing about the platform is that it provides something that did not exist until now: “What there was not “It was a system that was fully capable of mechanically altering the medium, the cells or the tissue. This technology makes it possible to sophisticate experimental systems and add complexity that was impossible until now.”