Nanomechanical analysis of cells from cancer patients

A multidisciplinary team of scientists from the University of California, Los Angeles (UCLA), were able to differentiate metastatic cancer cells from normal cells in patient samples by utilizing a modified form of atomic force microscopy (AFM) to measure the softness of the cells.

The study, published in the journal Nature Nanotechnology, represents a move toward applying novel technologies to better understanding the implications of altered cell architecture and its role in cancer progression.

The authors demonstrate that metastatic tumor cells may be more flexible than normal cells because of their ability to enter the bloodstream and maneuver through tight anatomical spaces. These spreading, invading cancer cells can cause a buildup of fluids in body cavities such as the chest and abdomen, but fluid buildup in patients does not always mean that cancer cells are present. If the fluid could be quickly and accurately tested for the presence of cancer, oncologists could make better decisions about how aggressive treatment should be whether any treatment is necessary. Conventional diagnostic methods detect only about 70 percent of cases where cancer cells are present in the fluid.

In this study, researchers collected fluid from the chest cavities of patients with lung, breast, and pancreatic cancers, a relatively noninvasive procedure. The UCLA investigators, led by James Gimzewski, Ph.D., used an AFM to probe differences in cell softness between metastatic and normal cells. The AFM uses a minute, sharp tip on a spring to push against the cell surface and determine the degree of softness, in much the way that a doctor’s hands might palpate the body during a physical examination.

“You look at two tomatoes in the supermarket and both are red. One is rotten, but it looks normal,” Gimzewski said. “If you pick up the tomatoes and feel them, it’s easy to figure out which one is rotten. We’re doing the same thing. We’re poking and quantitatively measuring the softness of the cells.”

After probing a cell, AFM assigns a value that represents how soft a cell is based on the resistance encountered. The team found that cancer cells were much softer than normal cells and that they were similarly soft, with very little variation in gradation. The normal, healthy cells from the same specimen were much stiffer than the cancer cells, and in fact, the softness values assigned to each group did not overlap at all, making diagnosis using this nanomechanical measurement easier and more accurate.

The UCLA team is now exploring whether nanomechanical analysis can be used to personalize cancer treatment based on the characteristics of a patient’s cancer cells. The idea would be to test a panel of appropriate anticancer drugs to see which would increase the stiffness of the cells from a particular patient.

This work, which was supported in part by the NCI, is detailed in the paper “Nanomechanical analysis of cells from cancer patients.” An abstract of this paper is available at the journal’s Web site.