The Cellular Sense of Touch

What image comes to mind when you hear the word "cell"? Some might imagine a photograph of a plant cell seen through a microscope, or a beautiful image rendered with the latest CG. In textbook terms, a cell is defined as "the basic unit of life that constitutes all living organisms." When magnified with a microscope, both plants and animals reveal their cells. The human body, too, is said to be made up of about 60 trillion cells. While cells come in various sizes, a single cell is typically about several tens of micrometers (µm), a scale similar to the thickness of a human hair.

Even when removed from the human body, cells can be kept alive in an artificial environment if maintained at the proper temperature and supplied with nutrients, tricking them into thinking they are still inside the body. This is what is known as "cell culture." When these cells cultured outside the body are observed closely under a microscope, you'll find that they are actually quite active. They move around and frequently pull on the objects they are in contact with.

The fact that cells pull on surrounding objects with strong forces, sometimes deforming them, has actually been known since the 1980s. At the time, however, attention was focused on the properties of the molecules inside the cell, and the role of the forces exerted by cells did not receive much notice. However, a turning point came around the year 2000. With the spread of microfabrication technology into the field of biology, experimental tools were created that allowed cells to push and pull (like a micro-sized training gym for cells). It was then successively revealed that cells respond to inputs such as "force" and "shape" to switch on various behaviors like programmed cell death and differentiation—in other words, that they possess a "sense of touch." What kind of information is "force" to a cell? What role does the cellular "sense of touch" play in maintaining human health or in disease? To find answers to these various questions, researchers from diverse fields such as biology, physics, chemistry, mechanical engineering, and medical sciences came together, giving rise to the interdisciplinary research field of mechanobiology.

In our laboratory, we are studying the mechanism by which cells recognize gently curved surfaces with radii ranging from several hundred micrometers (µm) to a few millimeters, a specific aspect of their tactile sense. For a long time, such gently curved surfaces, tens to hundreds of times larger than the cells themselves, were thought to be perceived by cells as simply flat planes. However, when we actually fabricated such curved surfaces and cultured cells on them, it became clear that the cells move dynamically across them and alter their behavior dramatically compared to on a flat surface, such as by changing the amount of protein they produce. By what mechanism is the shape of an object much larger than molecules and cells recognized by the cell? If this mechanism is elucidated, it may become possible to design innovative medical materials, for example, by applying various modifications to implantable devices like stents to prevent cellular pathologies. We are advancing our research with the aim of understanding the mechanism of the cellular "sense of touch" and creating new technologies to control cell behavior through "mechanics."