Engineering the interface between lipid bilayers and inorganic materials
- Understanding and engineering the interface between living matter and synthetic materials can enable technological advances in the areas of biosensors, therapeutics and diagnostics. One of the most crucial and commonly encountered class of such interfaces is the one between the cell membrane and various engineering materials and nanostructures. These interfaces can either be `large area' interfaces between the membrane and material surfaces or nanoscale `through thickness' cross-sectional interfaces that are formed as a synthetic material penetrates the membrane. This thesis describes contributions towards the understanding and/or development of each of these two kinds of interfaces. In the first two chapters, the focus is on synthetic membrane systems which provide a promising platform for biosensing applications. These are based on `large area' interfaces with engineering materials. One powerful approach consists of a synthetic lipid bilayer supported on an inorganic substrate. The non-covalent interactions between the lipids and the underlying substrate are of prime importance in these systems. Lipid spreading experiments, which measure the displacement, velocity, and roughness of the bilayer edge or the dynamic wetting line as it expands on the substrate, have proved useful in studying this interaction. However, previous spreading experiments have not observed any effects due to the inherent elasticity of the bilayer on expansion dynamics. To investigate this, dynamic expansion measurements of a phospholipid bilayer supported on substrates with different surface chemistry were performed. Remarkably different interface dynamics were observed on silica and chromium oxide surfaces. While the bilayer edge on silica monotonically roughened with expansion similar to other quenched noise 2-d systems, it showed a unique rough-smooth-rough interface transition on the chromium oxide substrate. This transition was found to be a result of the viscoelasticity of the lipid bilayer and could be modeled using a modified Edward-Wilkinson equation, which includes a spring-like term to account for the bilayer elasticity. These results demonstrate that the common lipid bilayer deposition technique of vesicle rupture generates supported lipid bilayers which are under compressive stress. This has important implications for biophysical studies performed on supported lipid bilayers and also for the stability of certain biosensing architectures like the pore spanning bilayer system. In the subsequent chapters, the emphasis is on developing a nanoscale `through thickness' interface between the cell membrane and synthetic nanostructures. The primary objective is to form an electrical interface with the interior of the cell for electrophysiological measurements. Such an interface is promising for various fundamental biophysical studies and also for applications such as high resolution neural prosthetics, on-chip electrically addressed artificial neuronal networks and chip based patchclamps. The main challenge in developing such interfaces is controlling the structure and properties of the junction between the device and cell membrane. Recent advances in nanoscale materials have enabled interactions at length scales natural to biology, thus providing an opportunity to control the structure of such junctions. By utilizing the design principles of transmembrane proteins that span the cell membrane, biomimetic metallic electrodes capable of penetrating the cell membrane can be developed. To elucidate the molecular structure of the electrode-membrane interface, coarse grained molecular dynamics (MD) simulations were carried out. These simulations revealed striking trends in interface structure for devices with different geometry and were used to optimize certain device parameters. Furthermore, energetics of the cell-device interaction were computed using thermodynamic integration and adiabatic switching to quantify the spontaneity of interaction. In the process, a unique methodology to compute the energetics of processes involving the interaction of nanostructured materials with soft matter structures was developed. In addition to these simulations, a physical model of cell deformation was developed to understand the mechanics of cell-device interaction. This was built on principles of continuum mechanics under a few simplifying assumptions. In addition to bringing down the parameter space for device design, this model explained a previously observed non-linear to linear transition in thin shell deformation experiments. Nanoscale `stealth' probed based on biomimetic design principles were fabricated using sophisticated microfabrication techniques. The electrical properties of the device were determined by performing cyclic voltammetry in a buffer solution with electrochemically active species. The formation of a well controlled junction between the post electrode and cell membrane was demonstrated by testing the device with red blood cells. A giga-ohm seal was observed to form spontaneously as the cell was brought close to the post, confirming intracellular access. The formation of giga-ohm seal is critical for patchclamping, a technique used extensively in the pharmaceutical industry. Together, MD simulations and cell deformation model provide a powerful approach to modify the device design depending upon the specific application. When coupled with the sophisticated yet flexible fabrication scheme developed for the device, the next generation of massively parallel and highly efficient interface between cells and electronics can be developed.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Stanford University, Department of Materials Science and Engineering
|Melosh, Nicholas A
|Melosh, Nicholas A
|Shenoy, Krishna V. (Krishna Vaughn)
|Shenoy, Krishna V. (Krishna Vaughn)
|Statement of responsibility
|Submitted to the Department of Materials Science and Engineering.
|Thesis (Ph.D.)--Stanford University, 2011.
- © 2011 by Piyush Verma
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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