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August 24, 2007

Observing single cells on the move

Researchers hold a key to studying cancer, wound healing and development

Figure 1: Using UV light to generate an adhesive patch for a single cell on a coverslip (left panels), then initiating its migration by creating a pathway (right panels).

© JACS/American Chemical Society/129/6694 (2007)

A team of researchers from RIKEN and other Japanese research institutions has developed a flexible technique for studying migration behavior of single cells. It relies on guiding cell movement by creating adhesive pathways through a non-adhesive environment using a light-driven reaction.

With their technique, the researchers are able to study details of the mechanics of how individual cells move. Already, for example, the team has been able to determine that cells which move by extending a broad front known as a lamellipodium travel faster than cells which can only use the much narrower filopodium.

The study is significant as migration of cells is fundamental to important medical processes such as growth and development, wound healing and the spread of cancer. In addition, the new technique allows researchers to guide individual cells into position, thus engineering nerve networks, for instance.

In the past, migration has been investigated using methods involving monolayers of cells. But cells within layers are unavoidably squeezed into different shapes and orientations and contact variable numbers of other cells, all of which affect movement. So the research team from RIKEN’s Discovery Research Institute in Wako, the Japan Science and Technology Agency, and Waseda and Kanagawa universities set about developing a way of studying the motion of individual cells in isolation, free from these influences.

In a recent paper, the researchers describe coating a glass coverslip with a compound to which cells cannot stick1. The chemical nature of this surface can be changed into one to which cells can adhere by exposure to ultraviolet light. And this can be done with great precision.

The team then prepared coverslips with adhesive patches just big enough for a single fibroblast cell (Fig.1). Leading from those cells they created pathways of adhesive surface in two forms—a broad form, the same width as the patch, which could accommodate lamellipodia, and a narrow pathway, one fifth the width, only fit for filopodia.

Movement of the cells could be followed under a conventional fluorescent microscope. When presented with a broad pathway, less than 10% of the cells extended filopodia. And those cells which used filopodia for movement traveled only about 80% as fast as those employing lamellipodia.

“We now want to combine this technique with advanced fluorescent microscope technologies to observe the molecular events in migrating cells,” says one of the project leaders, Jun Nakanishi. “We are also hoping to engineer neuronal networks by applying our technique to control the movement of single cells.”

References

  1. Nakanishi, J., Kikuchi, Y., Inoue, S., Yamaguchi, K., Takarada, T. & Maeda, M. Spatiotemporal control of migration of single cells on a photoactivatable cell microarray. Journal of the American Chemical Society 129, 6694–6695 (2007). | | (Link)