Multifunctional Nanoscale Surfaces for Biological ApplicationsPublic
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Tailoring the design of surfaces and interfaces with nanoscale features has the ability to significantly impact biological functions for a swath of applications including drug delivery, structure assembly, and biomedicine. For example, creating spatially defined nanoscale patterns has been known to contribute to changes in cellular architecture and mechanical properties, which are crucial to regulate cell behaviors ranging from cell adhesion, migration, differentiation, proliferation and intracellular signaling pathways. Nanolithography and nanopatterning techniques are frequently used for re-establishment of physiochemical interface to aid the understanding of cell-extracellular matrix (ECM) interactions. Among all the techniques, dip-pen nanolithography (DPN) and polymer pen lithography (PPL) are tip-directed patterning techniques suitable for molecular patterning due to their desire attributes such as high resolution, ink and substrate versatility and precise registration. Chapter 1 introduces focal adhesions, the current tools for studying mechanobiology, and existing ligand patterning techniques. Chapter 2 demonstrates how the cell endocytic fate is regulated by actomyosin mechanical forces, which can be tuned by subcellular cues defined by PPL. Moreover, the PPL based designs enable the generation of various myosin contractility profiles which subsequently alter mechano-sensitive signaling pathways that ultimately influence the number of caveolae and clathrin coated pits. In chapter 3, we implement DPN and PPL to generate metal phenolic network nanopatterns as a versatile platform for a broad range of applications, ranging from on-site nanoparticle synthesis to cell engineering and DNA mediated assembly. Finally, Chapter 4 summarizes the dissertation and provides an outlook on future research directions, including the development of a single cell screening tool and spherical nucleic acids that utilize metal phenolic networks. Together, the generality of these technique are useful for a wide variety of applications in ECM related diseases, complex biological systems, or surface functionalization for catalytic, chemical, biological sensing, and template-directed assembly.