This artist’s conception depicts the use of an atomic force microscope (AFM) to study the mechanical properties of cells, an innovation that might result in a new way to diagnose disease and study biological processes. Here, three types of cells are studied using the instrument: a rat fibroblast is the long slender cell in the center, an E coli bacterium is at the top right and a human red blood cell is at the lower left. The colored portions show the benefit of the new technique, representing the mechanical properties of the cells, whereas the gray portions represent what was possible using a conventional approach. Image: Purdue University/Alexander Cartagena |
Researchers are making progress in developing a system
that measures the mechanical properties of living cells, a technology that
could be used to diagnose human disease and better understand biological
processes.
The team used an atomic force
microscope (AFM) to study three distinctly different types of cells to
demonstrate the method’s potentially broad applications, says Arvind Raman, a
Purdue University professor of mechanical engineering.
For example, the technique could be used to study how
cells adhere to tissues, which is critical for many disease and biological
processes; how cells move and change shape; how cancer cells evolve during
metastasis; and how cells react to mechanical stimuli needed to stimulate
production of vital proteins. The technique could be used to study the
mechanical properties of cells under the influence of antibiotics and drugs
that suppress cancer to learn more about the mechanisms involved.
Findings have been posted online in Nature Nanotechnology and will appear in print. The work involves
researchers from Purdue University and the University of Oxford.
“There’s been a growing realization of the role of
mechanics in cell biology and indeed a lot of effort in building models to
explain how cells feel, respond and communicate mechanically both in health and
disease,” says Sonia Contera, a paper coauthor and director of the Oxford
Martin Programme on Nanotechnology and an academic fellow at Oxford physics.
“With this paper, we provide a tool to start addressing some of these
questions quantitatively: This is a big step.”
An AFM uses a tiny vibrating probe to yield information
about materials and surfaces on the scale of nanometers. Because the instrument
enables scientists to “see” objects far smaller than possible using
light microscopes, it could be ideal for “mapping” the mechanical
properties of the tiniest cellular structures.
“The maps identify the mechanical properties of
different parts of a cell, whether they are soft or rigid or squishy,”
says Raman, who is working with doctoral student Alexander Cartagena and other
researchers. “The key point is that now we can do it at high resolution
and higher speed than conventional techniques.”
The high-speed capability makes it possible to watch
living cells and observe biological processes in real time. Such a technique
offers the hope of developing a “mechanobiology-based” assay to
complement standard biochemical assays.
“The AFM is the only tool that allows you to map the
mechanical properties—take a photograph, if you will—of the mechanical properties
of a live cell,” Raman says.
However, existing techniques for mapping these properties
using the AFM are either too slow or don’t have high enough resolution.
“This innovation overcomes those limitations, mostly
through improvements in signal processing,” Raman says. “You don’t
need new equipment, so it’s an economical way to bump up pixels per minute and
get quantitative information. Most importantly, we applied the technique to
three very different kinds of cells: bacteria, human red blood cells, and rat
fibroblasts. This demonstrates its potential broad utility in medicine and
research.”
The technique is nearly five times faster than standard
AFM techniques.
