Study of Dynamical Mechanical Properties of Pericellular Layer

Tufts University, Medford MA

Investigators

Abstract

This project will develop novel tools to study physical properties of individual biological cells at the nanoscale. The properties of a brush-like part of cells that covers the cell body of most cells have remained unknown. This is interesting because it is known that the biological changes in this brush layer are correlated with many human diseases, like cancer, cardiovascular diseases, and even aging. This work will support the development of experimental and theoretical methods to study the physical properties of this brush layer on individual cells. The developed methods will be applied to study cells of one of the most puzzling creatures, naked mole rats, which are long-lived and highly resistant to cancer. This study of age-related changes in the brush layer may eventually shed light on the mechanisms responsible for the exponential increase in the prevalence of certain diseases (including cancer) associated with aging. This multidisciplinary work will combine expertise from physics, engineering, and biology of researchers from three different institutions and have a positive impact on engineering education. Atomic force microscopy will be used to develop a novel high-resolution experimental method to measure the dynamical mechanical properties of the pericellular layer surrounding cells. The project's approach arises from a novel technique, Fourier-transform dynamical mechanical analysis, a fast high-resolution quantitative method will allow for measuring frequency-dependent storage and loss moduli at the subcellular level. These mechanical properties are expected to be highly nontrivial. Therefore, it is expected that advanced mechanical models, such as various viscoelastic and poroelastic contact models, will be necessary. These models will be investigated and compared with the experimental results to understand the physical and mechanical nature of the pericellular brush layer. The research team will apply the developed methods to study the mechanics of the pericellular layer of fibroblasts of naked mole rats. The difference between these animals and other rodents like the guinea pig, rats, mice will be investigated to learn the aging-related changes in naked mole rats in comparison with regular aging rodents. The importance of particular polysaccharides, such as hyaluronic acid, for the mechanics of the pericellular layer will be studied. It will fill the gap in our knowledge on the specific features of mechanics of the pericellular layer of naked mole rats and contribute to the physics of cancer and longevity. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.