Diagnostics & Imaging Week Washington Editor

Researchers at the Massachusetts Institute of Technology (MIT; Cambridge) have come up with a novel approach to obtaining images of the incredibly minute — and incredibly important — features of cell surfaces, but they are not relying on photons to generate those images.

Instead, the researchers are making use of small probes to pick up the interaction between antibodies and cell surfaces to generate a map of cell surfaces, with the resulting data potentially enabling researchers to infer something about the structure of the cell membrane as well as the role of mechanical force in cell physiology.

In a paper published in the June 5 edition of the Proceedings of the National Academy of Sciences, Sunyoung Lee, a doctoral candidate at MIT, and several others described the use of functionalized force imaging (FFI) to map the interaction between vascular endothelial growth factor receptor 2 (VEGFR2) and an antibody specific to that receptor, which allows the researchers to accurately map out the location of the VEGFR2 receptors on the cell surface.

FFI has been previously employed to measure the binding force in proteins isolated from cells, but this effort shows that the interaction can generate a picture of chemical binding. However, the instrument used to measure all this has to be somewhat sensitive, to put it mildly. The amount of energy needed to bind the antibody to the VEGFR2 receptor is roughly 100 piconewtons.

(A newton is the force required to accelerate a one-kilogram mass by a meter per second for each second the force is applied, and a piconewton is one-trillionth of a newton.)

Krystyn Van Vliet, PhD, assistant professor of materials science at MIT's Department of Materials Science and Engineering, told Diagnostics & Imaging Week that "the antibody molecule is hung from a cantilever made of silicon nitride, which is tens of microns long."

She compared the assembly to a record player arm and needle, "and we dangle the antibodies from that needle."

One might wonder how many of her students have ever seen, let alone used a phonograph, but a better question might be: How does all this generate images?

"We're shining a laser on the back of the cantilever, and when the laser light bends, that tells us that the cantilever is oscillating," Van Vliet said.

The team picked up the patterns of those reflections of laser light with an atomic force microscope, which Van Vliet said is commercially available from Molecular Imaging, a company bought by Agilent Technologies (Palo Alto, California) in 2005.

For better or for worse, this technique is unlikely to make its way directly into clinical use for patients any time soon.

Van Vliet, senior author of the study, said, "I think because of the sensitivity of the equipment right now, that's not in the foreseeable future," citing fluid flow in the body as one of the things that would be difficult to compensate for.

Still, this approach could yield some very useful diagnostics instruments and applications, especially given that the preliminary work focused on one of the vascular endothelial growth factors, which many researchers think is perhaps the most useful vector for attacking tumors.

"You could use a tool like this to screen for drugs" that bind most efficiently to the VEGFR2 receptor and cut down on the time and expense involved in testing, Van Vliet said.

As for the regulatory status of this technique, Van Vliet said that the use of an atomic force microscope requires no new algorithm to sort out the code hidden in the laser light reflections. However, the regulatory status of the nanoprobe may be a different matter.

Much of the emphasis at the Department of Materials Science, Van Vliet said, is on how mechanical forces affect cell structure and function, how stiff cell membranes are, and how that rigidity modulates function.

"Nobody understands how stiffness drives cell function," she said, but many of those barriers seem sure to fall soon to the energy and inventiveness of modern scientists.

Methodist Hospital (Houston), the University of Houston (Houston), and Weill Cornell Medical College (Ithaca, New York) reported last week that they are teaming up to found the Institute for Biomedical Imaging Science (IBIS). The three institutions will blend their respective areas of expertise to push biomedical imaging further along by crafting a series of interdisciplinary programs and by forging several joint training programs to produce the next generation of basic and applied scientists.

King Li, MD, director of the new institute and the chief of radiology at the Methodist Hospital, said that he possibilities for collaborative research by this consortium "are endless — we hope to attract research grants that will lead to discoveries in new technologies and techniques to better unearth diseases at their earliest stages."

Ioannis Kakadiaris, chair of the IBIS steering committee and the director of bioimaging and biocomputation at the University of Houston, said the three institutions "are establishing a unique research environment, with as many as 50 scientists working together … that already are aligned through academic affiliations." Kakadiaris said the effort would position the new institute "on the forefront of discoveries in biomedical imaging."

At least two of the three schools are heavily funded of late.

The Methodist Hospital Research Institute reported earlier this year that it had broken ground toward a new facility of 420,000 square feet that will be dedicated to advanced medical research. Funded in part by a $100 million endowment, the building is expected to be finished in autumn 2009 and will include space for state-of-the-art imaging, including molecular imaging, medical genomics and medical proteomics.

Weill Cornell recently reported that it had nailed down gifts totaling $400 million, part of which will go to fund a proposed biomedical research building.