Biomechanics of the Cell Plasma Membrane: The effect of shear stress and cell stiffness on temporary cell permeabilization

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Modern biotechnology and biomedicine are dependent on passing normally impermeable molecules like DNA and drugs into cells. Physical methods of gene transfer rely on mechanically disrupting the cell plasma membrane, temporarily, to allow the transport of molecules into the cell. The cell plasma membrane is a complex cell structure. We understand very little about the physical forces associated with temporary permeabilization and mechanics of the cell (biomechanics). Recently my lab has discovered a simple physical method to temporarily permeabilize adherent cells. This technique uses the forces created by an inert jet of gas to create temporary pores in the cell plasma membrane. The long term objective of my research program is to be able to quantify and manipulate the biomechanical properties of the cell to identify and change biochemical and physiologic properties. Over the next 5 years my laboratory will further develop our gas jet method and use it to understand the biomechanics of the cell plasma membrane. We will use computer simulations and flow visualization experiments to define the forces created by our device. The dependence of pore formation on the mechanical properties of the cell will be investigated. We will also validate the dependency of temporary pore formation by recreating similar forces in other experimental setups. The research will further develop a simple, inexpensive method for transferring genes and other macromolecules into cells without the need for viral vectors or cytotoxic drugs. The discoveries of this research program could be used to improve yields in biotech industries and provide researchers with new tools and techniques to study cell biology.