Shanghai Xinfan Bio: Cell Migration Analysis - Huaqiang Electronic Network

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Cell migration is a complex process that means cells are free from binding, moving within the body, and invading new tissues. However, research on cancer cell migration faces unique challenges. A tumor is a heterogeneous group, and only a small fraction of cells can acquire the characteristics of migration and move to new tissues. Depending on the microenvironment, the metastatic cells exhibit a fickle migration pattern.

As a result, researchers face tough choices when studying migration. On the one hand, they need a simplified in vitro system to test specific hypotheses and mechanisms for analysing motion. On the other hand, they want to study these mechanisms in the context of organization and living. This contradiction has prompted more and more researchers to turn to three-dimensional (3D) models and in vivo imaging techniques.

3D modeling

Many of our understanding of cells comes from 2D experiments. However, the molecular mechanisms observed through 2D experiments do not necessarily lead to the right answer. According to Kenneth Yamada of the National Institute of Dental and Craniofacial Research, it is now clear that a significant portion of the 2D conclusions may not apply to 3D systems. There are differences in the biophysical mechanisms of signal transduction, cell morphology, and cell migration.

Peter Friedl of the Institute of Molecular Sciences in Nehmegen, the Netherlands, believes that the development of 3D models over the past decade is crucial for the study of cell migration. These complex models allow researchers to control factors such as the pore size and stiffness of the scaffold, which may be important for cell movement. Recently, Yamada's team discovered a new migration mechanism in normal and tumor cells, in which cells move forward using a piston-like core.

Microfluidic device

Microfluidic devices and sandwich analysis are another important way to test the migration hypothesis. Mingming Wu is a bioengineer at Cornell University. Eight years ago, her lab developed an agarose gel microfluidic device. “If you want to see how the fish swim, it's best to put them in the aquarium instead of the sea,” she described the importance of microfluidics.

According to Wu, microfluidics overcome some of the shortcomings of the classic Boyden chamber. Through the Boyden chamber, researchers can observe how cells respond to chemical signals. However, for cancer cells, it also has limitations. "You can't observe the behavior of individual cells through it, which is important for cancer." Microfluidic devices are about the size of cells and control the flow of liquids and compounds in tiny channels.

Mammalian model

Over the past decade, research on cell migration has shifted from a basic mechanism to disease pathology. Previously, relying on transparent animals such as nematodes and zebrafish, people have gained basic insights into the migration of cells in the body. Nowadays, people are beginning to face difficult challenges with mammals as their research goals. Of course, this is very difficult. Mouse tissue is opaque, visible light can only penetrate 100 microns, and generating a certain number of mouse models is expensive and time consuming.

Despite this, more and more researchers are using in vivo imaging techniques to study cell migration in mice. This technique relies on transgenic mice and fluorescent reporter molecules that display tumor cells, which are then tracked using a microscope.

To penetrate the mouse, the researchers used an image window that was surgically implanted into the transparent entrance of the mouse tissue. They can implant these viewing windows on the back skin folds, near the breast, and on the abdomen. Through multiphoton microscopy, researchers use longer wavelength, more penetrating infrared and far-infrared light to activate reporter molecules to achieve millimeter depth in mouse tissue.

In addition, cell migration has attracted computational biologists and mathematical modelers. Areas such as mathematics and migration analysis are merging. Some researchers use computational work to simulate the 3D environment of cells and how they affect the organization and movement of cells. This highly controlled system allows researchers to generate new hypotheses and build new experiments to test them.

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