Skin cells migrating to heal a wound have been observed in fine detail thanks to a novel form of microscopy developed by physicists in Taiwan. The method involves tracking tiny waves rippling along the surface of moving cells and the researchers say that their findings could help to identify the structures that enable cells to move.
There are many biological processes – including the spreading of cancer – that involve individual cells moving on their own accord. In one common form of this “motility”, a cell extends one or more feelers that can stick to their surroundings and pull the main cell body along.
Stretchy skin
Skin cells surrounding an open wound release a number of bio-factors that create a chemical gradient towards the exposed region. Sensing these chemicals, cells including “fibroblasts” extend a part of their bodies, called protruding edges, towards the open region.
Due to the relatively high concentration of motor proteins called myosin in the central region of these protrusions, the structures tend to stretch at a varying rate along their length. In many cases, this causes the protrusions to fold up at their edges triggering a surface wave known as an “edge ruffle”.
Various research groups have observed these waves as they propagate backwards from the edge of a migrating skin cell. However, the physical details of these waves are still poorly understood, not least because the amplitudes are of the order 100 nm, the wavelengths are just a few microns and cell membranes are almost transparent when isolated in a suitable culture. In addition, any measurement must be carried out very carefully to avoid perturbing the motion of membranes.
Membrane waves
In this latest work, a group of researchers led by Chau-Hwang Lee of Academia Sinica in Taiwan has quantified the membrane waves for the first time using a microscopy technique that they developed back in 2002. Reflecting intense light off a skin cell sample grown on a glass slide, the researchers track the evolution of a skin cell through slight variations in the intensity of light in a process they call “non-interferometric wide-field optical profilometry”.
Taking measurements on 23 human fibroblast cells, the researchers recorded membrane waves with amplitudes up to 300 nm. The varying acceleration was also observed as the waves speed up from 10 nm s–1 at the edges to 25 nm s–1 after 20 µm. These results confirmed a simple model put forward by a separate group of researchers two years ago.
“Cell migration is important in many aspects, from wound healing to cancer metastasis,” said Chau-Hwang Lee, a member of the research team. “Because membrane waves are significant features of cell motility, biologists may want to use them as a signature to understand the motility of specific cells.”
‘Cute’ technique
Stephen Curry, a biophysicist at Imperial College, London is impressed by the optical ingenuity of the new experiment. “It looks like quite a cute optical technique because they can measure variations in the topography of the upper surface of the cell which are shorter than the wavelength of the light used to illuminate the sample.”
Curry cautions, however, that there are limitations of using skin isolated from the body. “While such cells, grown on glass slides, provide a good model system for looking at some aspects of cell behaviour, it is difficult to transfer observations to inferences about wound healing in real human beings.”
Lee told physicsworld.com that he and his colleagues intend to create a more realistic testing ground by repeating the observations for skin cells isolated in a cell-culture chip. He also intends to work with theorists to develop a more accurate quantitative description.
This research will be published in Physical Review Letters.
