Engineering cell access using nanostraws
- The study of biology is driven by our ability to perturb biological systems and observe the outcomes. At the cellular level, by predicting the presence of a biological interaction and perturbing elements of that interaction, we increase our understanding of how a cell functions. Interactions between biomolecules consist of binding events, enzymatic breakdown, metabolic synthesis, and many others, but one valuable distinction between interactions is the locale, which can be extracellular or intracellular. Extracellular signals allow cells to interface with their environments including other cells and soluble signals, but the majority of signaling events occur intracellularly. To protect the integrity of the cell, the cell membrane tightly regulates the passage of molecules, which provides a robust barrier between the extracellular and intracellular space. Therefore, perturbing intracellular elements of the cell effectively requires a method for accessing the cell without disruption. One strategy for passing material through the cell membrane is to use the cell's natural uptake mechanisms, thereby limiting the disruption to the cell. Unfortunately, methods which leverage endocytosis or other uptake mechanisms can do little to protect the cargo from the cell's inherent defense mechanisms. An alternative strategy is to physically deliver material into the cell by creating gaps in the cell membrane. Until recently, this was difficult because small nanometer scale gaps could not be reliably formed in cells. However, advances in fabrication have allowed nanometer scale objects to be reliably produced, which have demonstrated promise as a pathway to cell access. This thesis describes the development of a technique based on high aspect ratio hollow nanowires, called nanostraws, which we use to deliver material into cells. Compared to other nanowire techniques, nanostraws are capable of timed delivery, which provides a powerful, unique lever in engineering cell access. Beginning with fabrication, we discuss the types of nanostraw devices used for delivery and we characterize cell behavior on the nanostraws. Later, we apply the nanostraw devices to study a point of controversy in the field of nanowire delivery, the question of whether or not nanowires penetrate into cells. This study is complemented with studies of cell behavior or adhesion and their effects on delivery. We then use the nanostraws to observe the effects of perturbing the cell cytoskeleton on delivery and penetration. This thesis concludes with a discussion of the field of nanowire delivery at large, and future directions for nanowires and nanostraws in particular.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Stanford University, Department of Materials Science and Engineering.
|Melosh, Nicholas A
|Melosh, Nicholas A
|Statement of responsibility
|Submitted to the Department of Materials Science and Engineering.
|Thesis (Ph.D.)--Stanford University, 2015.
- © 2015 by Alexander Minyi Xu
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