The research supported by this SGER award addresses the quantification of the response of the in vivo cell membranes probed with Atomic Force Microscope (AFM). The long-term objective is to understand the extent to which the membrane of a cell mirrors certain biochemical processes within the cell and how the biophysical properties of the membrane provide insight into the health of a cell. At the heart of such an investigation is a theory capable of modeling the complex interaction between an AFM probe and the soft cell membrane. Such a theory then renders the AFM a powerful tool for characterizing the biomechanical properties of cell membranes.
The investigation proposed here is based on a general continuum theory derived from first principles of fluid membranes endowed with local bending resistance. In accordance with the physics of the problem the membrane is assumed to enclose a fluid medium, which transmits hydrostatic pressure to the membrane, and a point load is applied at the pole of the membrane to simulate the effect of an AFM probe. Both types of loading are associated with a potential and the problem is then cast in a variational setting, which is used to obtain the equations that describe axisymmetric equilibrium states of the cell membrane. Further refinements associated with global constraints on the enclosed volume and contact with a rigid substrate are proposed together with a solution strategy that relies on an iterative scheme for calculating the associated Lagrange multipliers. The main goal then is to use the numerical implementation of the model to identify the material constants associated with the mechanical behavior of the cell membrane through correlation with AFM data and further refinement of the model. The expected outcome of this seed grant project would be the first experimentally validated model that characterizes the nonlinear interaction between an AFM probe and a cell membrane.
The broader impact of the proposed research is the development of new technology for biological research, by including Atomic Force Microscope among the tools used in cell investigation. The proposed theoretical/computational approach together with the experimental program has far reaching potential applications. Using this method, the effect of pathogens on healthy cell membranes can be studied resulting in physical methods for identification and detection of these pathogens (for e.g. in developing defensive measures against biological and chemical agents). A promising area of investigation would be to investigate changes in the membrane of tumor cells that enable cells to divide and metastasize. This could potentially lead to earlier detection and confirmation of malignancy. Yet another fruitful avenue of research would be to use this method to gain a deep understanding of the underlying mechanics of cell motility. Finally this method could facilitate a deeper understanding of the relationship between membrane properties and disease, i.e. how changes in membrane properties and membrane-bound proteins leads to (or are indicative of) disease, which in turn could lead to alternative treatment strategies.
