Rheology is the science of studying how soft materials and complex fluids deform and flow under stress. These materials are everywhere in biology, and since their relative stiffness or squishiness is relevant to diseases, such as cancer, there is a need to accurately measure just how squishy they are.
Researchers at the University of Pennsylvania’s School of Engineering and Applied Science have made advances in the field of “microrheology,” developing a microscopy system able to make such measurements at previously impossible length scales.
By embedding cigar-shaped gold nanorods in the material to be studied and observing them with a stereoscopic, laser-based microscope, the researchers are able to make measurements on the order of 100 nanometers or smaller. This is small enough for the researchers’ microrheology technique to be used on the membranes of cancer cells.
They plan to apply this technique to ongoing research at Penn’s Physical Sciences Oncology Center (PSOC), which aims to connect the stiffening of liver cells in cirrhosis to the progression of liver cancer.
The researchers, John C. Crocker, professor in Penn Engineering’s department of chemical and biomolecular engineering, along with lab members Mehdi Molaei and Ehsan Atefi, published a study detailing this system in the journal Physical Review Letters.
“Our technique provides a unique way of probing the fluctuations and rheology of soft materials at the nanoscale for the first time,” Dr. Crocker said. “This has the potential to revolutionize experiments in soft matter and interfacial science, and provides experimental verification of dynamics that could only previously be observed in computer simulations.”
The researchers tested their technique on a model polymer with well-understood rheological properties, using a laser-illuminated dark-field microscope with two different polarizations to track the nanorods. Somewhat like a 3D movie, contrasting the data from the two polarizations allowed the researchers to calculate the rods’ orientation in space.
“The result turns out to be orders of magnitude superior to previous methods in several important metrics, including working on volumes of goo as small as an attoliter, or a quadrillionth of a milliliter,” Dr. Crocker said. “Still, the rods are way smaller than what can actually be resolved in an optical microscope; thousands could fit inside a single E. Coli. We had to solve a lot of optics calculations in order to quantitatively convert optical polarization to orientation.”
New research in collaboration with PSOC Director Dennis Discher, Robert D. Bent Professor of Chemical and Bimolecular Engineering, is already underway. Dr. Molaei is measuring the stiffness of liver cell membranes in vitro.