Toshiro Ohashi

Towards Better Understanding of Living Systems by Describing Cells from Viewpoint of Mechanical Engineering

Toshiro Ohashi , Professor

Faculty of Engineering, Graduate School of Engineering

High school : Kanagawa Prefectural Odawara High School

Academic background : Masters from the University of Tsukuba

Research areas
biomechanics
Research keywords
cells, mechanical stimulation, remodeling, micro mechanical testing, MEMS technologies
Website
http://leaf-me.eng.hokudai.ac.jp/LabHP/index.htm

What is your goal?

The goal of my study is to describe structure and functions of cells as the basic element of our bodies using the knowledge and technologies of engineering and contribute to the medical field by understanding cause of diseases and developing their treatment. Our bodies, consisting of approximately 60 trillion cells, are continuously subjected to a variety of forces, including gravity. For example, large forces are applied during exercise. Furthermore, there are various flows inside the body, such as blood flow andinterstitial flow, subjecting neighboring tissues to flow-derived forces. In other words, it is understood that our bodies are under more or less continuous mechanical stimulation. Knowledge of Strength of Materials and Hydrodynamics as the basis of mechanical engineering will prove useful in understanding these forces. Thus, studying how cells modulate structure and functions in response to mechanical stimulation will give us a deeper understanding of life phenomena. Let us consider a specific example. Figure 1 illustrates forces applied to the knee joint. During motion, in addition to gravity, complex forces such as compression and torsion are generated. Cartilage cells continuously subjected to these mechanical stimulations are responsible for maintaining cartilage tissues in a normal state. This research field in which human body is studied from the viewpoint of Mechanical Engineering is known as “Biomechanics” and has seen increasingly active research around the world in recent years. In addition, it is also expected to contribute to the medical field as it has become increasing clear that cell-level responses are closely related to the occurrence of diseases.

 

What equipment do you use and what experiments do you carry out?

Figure 2 is a microscopic photograph of cells. These are vascular endothelial cells adhering to the lumen of blood vessels. We observe them using a microscope because they are extremely tiny structures measuring approximately tens of μm in size (1 μm being 1/1000 mm), as the scale at the bottom right of the picture indicates. The white parts are structures that determine the shape of cells, known as cytoskeleton and regarded as the bones of cells. In fact, this cytoskeletal structure is known to dynamically respond to mechanical stimulation by becoming thicker or being rearranged in a certain direction. This response mechanism is known as the remodeling of cells. This mechanism is considered the same as the one by which exercise makes our muscles and bones stronger.

 

 

 

State-of-the-art microscope technologies are utilized to observe the manner of this remodeling and the changes in stiffness caused by remodeling. To determine the stiffness of tiny cells, micro mechanical testing technologies are needed. One such example is the micropipette aspiration technique (Fig. 3(a)). The surface of a cell can be suctioned using a glass micropipette with an inside diameter of approximately 10 μm to determine the stiffness of the cell. The cytoskeletal structure of cartilage cells before suction is observed using a specialized microscope called a fluorescence microscope to obtain the data in the upper side of Fig. 3(b). This data can be subjected to image processing to make the cytoskeletal structure clearly emerge as in the lower side of Fig. 3(b).

Furthermore, since most cells exhibit characteristics of adhering to surfaces, it is important to measure the adhesive forces generated at adhesion in order to understand the mechanical environment of cells, with the expectation that this can also be applied to cell culture technologies in regenerative medicine. Figure 4 illustrates fine silicone micropillars (3 μm in diameter, 10 μm in height) created using micro electromechanical system (MEMS) technologies to measure this adhesive forces. For example, culturing vascular smooth muscle cells cause the micropillars to bend due to adhesive forces, enabling determination of the forces (Fig. 4(a)). The direction and length of the arrows indicate the direction and intensity of the adhesive forces of cells. The cytoskeletal structure at this time is shown in Fig. 4(b).

 

What developments will we see in the future?

Since cells (animal cells in this document) are a topic taught within the subject of Biology in high school, it was not until I completed a graduate course to start working as a researcher that I learned that there is a field in which cells are studied from an engineering point of view. Since science refers to a systematic body of knowledge and research methodologies, students at the undergraduate level will learn sciences with systems that have been sufficiently verified. The latest studies are carried out in graduation research by undergraduate students and Master’s and doctoral programs in graduate schools. I believe that taking a look at part of these studies will stimulate your intellectual curiosity. Therefore, I would like to sufficiently systematize the world of cells from an engineering point of view and develop it into the enjoyable, rewarding field of biomechanics. In addition, while no mention was made in this document, I also think that in going forward it will become increasingly necessary to develop applied biomechanics with a view to contributing to the medical field.

The goal of my study is to describe structure and functions of cells as the basic element of our bodies using the knowledge and technologies of engineering and contribute to the medical field by understanding cause of diseases and developing their treatment. Our bodies, consisting of approximately 60 trillion cells, are continuously subjected to a variety of forces, including gravity. For example, large forces are applied during exercise. Furthermore, there are various flows inside the body, such as blood flow andinterstitial flow, subjecting neighboring tissues to flow-derived forces. In other words, it is understood that our bodies are under more or less continuous mechanical stimulation. Knowledge of Strength of Materials and Hydrodynamics as the basis of mechanical engineering will prove useful in understanding these forces. Thus, studying how cells modulate structure and functions in response to mechanical stimulation will give us a deeper understanding of life phenomena. Let us consider a specific example. Figure 1 illustrates forces applied to the knee joint. During motion, in addition to gravity, complex forces such as compression and torsion are generated[A1] . Cartilage cells continuously subjected to these mechanical stimulations are responsible for maintaining cartilage tissues in a normal state. This research field in which human body is studied from the viewpoint of Mechanical Engineering is known as “Biomechanics” and has seen increasingly active research around the world in recent years. In addition, it is also expected to contribute to the medical field as it has become increasing clear that cell-level responses are closely related to the occurrence of diseases.