EAGER: Development of Methods to Study Dynamical Mechanical Properties of the Pericellular Layer of Cells

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The pericellular layer is an important but not fully studied part of cells. It covers the cell body of all mammalian cells and the majority of bacteria. Changes in this layer have been connected with many progressive diseases, including cardiovascular disorders, inflammation, and cancer. There is evidence that it is also important in aging. As has recently been discovered, this layer plays an important role in cell mechanics. Although static mechanical properties of this layer have recently become a subject of investigation, dynamical mechanical properties of this layer remain totally unknown. At the same time, these properties should define cell-cell interactions in many normal physiological and pathophysiological processes - including blood flow, invasion of cancer cells, and cell motion during stem cell therapy. The main reason for this gap in our knowledge is the lack of experimental tools to measure dynamical mechanical properties of the pericellular layer of cells. The research supported by this EArly-concept Grant for Exploratory Research (EAGER) award will focus on the development of such a transformative tool, which allows direct studying the dynamical mechanical properties of the pericellular layer of cells. This research involves both advances in hardware and advances in computational analysis necessary to make measurements at the nano and submicron level. The obtained experimental data will be analyzed to outline the mechanical nature of the pericellular layer. The overarching long-term goal is to use this new tool to study the role of the pericellular layer in cancer and aging. The research results will be incorporated into modules for teaching Materials and Bioengineering courses. This research will develop a dynamical mechanical analyzer, based on the atomic force microscopy platform, in which all frequencies are measured at the same time. The mode is called Fourier transform nanoDMA, or FT-NanoDMA. A novel feedback system will allow for precise controlling of the probe?sample interaction to measure storage and loss moduli of the pericellular layer as a function of frequency. A new mechanical model extracting the storage and loss from the nanoindentation measurements will be developed using Sneddon formalism . The device and the model will be verified using commercial ultrasoft polymers. The first experimental data of the dynamic mechanical properties of the pericellular coat will be obtained on fixed mammalian cells, which allow precise separation of the impact of the glyocalyx molecules and the corrugations of the pericellular membrane to the dynamic response of the pericellular brush layer. The data will be compared against existing mechanical models of cellular biomechanics. This knowledge will help to understand if the existing models can describe the observed data or if new models have to be developed.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.