Research
Research
Cell stiffness plays a pivotal role in cellular function and differentiation, serving as a physical indicator of changes in cell state, including phenomena such as cancer metastasis, pathogen infection, and immune cell activation. To assess cell stiffness, our laboratory has developed and utilized various techniques, such as atomic force microscopy, real-time deformability cytometry, and a dielectrophoretic platform. These tools enable us to compare the mechanical characteristics of different cell populations and identify sub-populations within complex samples.
In our previous research, we established a connection between cell stiffness in rubella virus (RV) infected cells and viral cytopathogenicity, cortical actin organization, and cell migration, shedding light on how RV manipulates host cells (Kräter M and Sapudom J et al. 2018 Cells). Additionally, we introduced a high-throughput dielectrophoretic platform to assess cell deformability (Menachery A and Sapudom J et al. 2020 Biotechniques). Using this platform, we demonstrated an increase in cellular stiffness in mature dendritic cells due to higher actin content, resulting in enhanced CD3-mediated T cell activation (Alatoom A and Sapudom J et al. 2020 Advanced Biosystems). This highlights the significant role of biomechanics in immune regulation.
In our laboratory, we plan to use cell stiffness as a monitoring tool to study cell behavior during various biological processes, such as cell differentiation and metastasis, and to diagnose pathological changes. However, because measuring cell stiffness outside their native tissues presents limitations, our goal is to develop a new image-based toolbox for quantifying the viscoelastic properties of individual cells within 3D biomimetic tissues. This will enable us to explore how the extracellular matrix impacts cell elasticity and cellular behaviors. Our approach not only involves comparing cell stiffness but also delves into the underlying mechanisms and their connection to biological function. We will employ molecular biology, imaging, biomimetic engineering, and machine learning techniques to gain a comprehensive understanding of cell mechanical regulation. Furthermore, this knowledge can have applications in clinical diagnostics and the assessment of therapeutic outcomes.
Mechanomemory – a new concept for improving adoptive cell therapy
As a researcher in the field of biomedical engineering, I am committed to developing innovative solutions for tackling the pressing challenges of global health. One area of particular interest for me is the development of a miniaturized lymph node model for biomedical study and applications. The ongoing threat of pandemics caused by viruses and bacteria has underscored the importance of rapid and effective responses to emerging infectious diseases.
One promising approach to combating these pathogens is the use of high specificity antibodies extracted from the blood plasma of recovered donors, also known as convalescent therapy. However, the transfusion process can cause side effects and obtaining suitable donors can be difficult, making this approach less than ideal.
To address these challenges, I am interested in developing a miniaturized lymph node model that can rapidly produce specific neutralizing antibodies against corresponding strains of viruses and bacteria while ensuring patient safety. By leveraging the latest advances in biomedical engineering and lab-on-chip technologies, my goal is to create a complete solution for healthcare that can be used to generate neutralizing antibodies on demand. The findings from this research can have far-reaching implications for the fight against infectious diseases and improve the overall health of people around the world.
Additionally, this miniaturized lymph node model has the potential to be used in various other biomedical applications, such as drug development and vaccine testing. By mimicking the complex microenvironment and cellular interactions of the lymph nodes, this model can provide a more accurate and reliable representation of the human immune system. Furthermore, it can also be used to study the mechanisms of disease progression and the effects of different treatments.
My research aims to study the effect of biophysical and biochemical cues on the fate regulation of immune cells, with a particular focus on investigating the concept of "mechanomemory." Specifically, I will study how topology, topography, stiffness, flow, matrix compositions, and other cues influence the mechano-sensing and fate regulation of immune cells in engineered 3D microenvironments. This research is particularly relevant as dysfunction in immune regulation can lead to the progression of several diseases that are often associated with changes in the mechanical properties of tissues.
The concept of "mechanomemory" refers to the observation that immune cells may retain a memory of the mechanical microenvironment they were previously exposed to, which affects their behavior and function when they are subsequently exposed to a new mechanical environment. This phenomenon has been observed in our previous studies of dendritic cells, but the underlying mechanism remains unexplored. Through this research, I aim to shed light on the underlying mechanism of mechanomemory and how it relates to the fate regulation of immune cells.
The ultimate goal of this research is to guide the fabrication of functional immune-modulating materials for medical applications, such as regenerative medicine, cancer treatment, and tissue engineering by understanding the role of mechanical memory of immune cells in the microenvironment. Additionally, this research will provide new insights into the underlying mechanism of immune dysfunction in diseases associated with changes in the mechanical properties of tissues.
As a researcher in the field of space biology and medicine, my goal is to utilize established biomimetic models and microphysiological systems to study the effects of microgravity on cell and tissue functions. By understanding how microgravity impacts the immune system, we can improve the well-being of astronauts and the success of space missions. However, the benefits of this research extend far beyond just the realm of space travel.
The insights gained from studying the effects of microgravity on the immune system can provide a deeper understanding of immune dysfunction due to aging on Earth. This knowledge can inform the development of new treatments and therapies for age-related immune deterioration, as well as other physiological conditions related to microgravity. Additionally, the research can also lead to the development of new technologies and techniques for space medicine, such as the design of more effective countermeasures to mitigate the negative effects of microgravity on human physiology and physiology.
Furthermore, this research can also have implications for regenerative medicine. By understanding the mechanisms of how cells respond to microgravity, we can potentially develop new strategies for tissue engineering and regenerative medicine on Earth.