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008 190718s2018 xx sbm 000 0 eng d
020 9780438371842
035 (MiAaPQ)AAI10845916
035 (MiAaPQ)uchicago:14528
040 MiAaPQ|beng|cMiAaPQ|dNTU
100 1 Parameswaran, Ramya
245 10 Silicon Nanowires for the Optical Modulation of Cellular
Activity
264 0 |c2018
300 1 online resource (154 pages)
336 text|btxt|2rdacontent
337 computer|bc|2rdamedia
338 online resource|bcr|2rdacarrier
500 Source: Dissertation Abstracts International, Volume: 80-
01(E), Section: B
500 Advisers: Bozhi TIan; Erin Adams
502 Thesis (Ph.D.)--The University of Chicago, 2018
504 Includes bibliographical references
520 One of the fundamental goals guiding research in the
biological sciences is to understand how cellular systems
process complex physical and environmental cues and
communicate with each other across multiple length scales.
Importantly, aberrant signal processing in these systems
can lead to diseases that can have devastating impacts on
human lives. Biophysical studies in the past several
decades have demonstrated that cells can respond to not
only biochemical cues, but also to mechanical and
electrical ones. Thus, the development of new materials
that can both sense and modulate all of these pathways is
necessary. Semiconducting nanowires are an emerging class
of discovery platforms and tools that can push the limits
of our ability to modulate and sense biological behaviors
for both fundamental research and clinical applications.
These materials are of particular interest for interfacing
with cellular systems due to their matched dimension with
subcellular components (e.g., cytoskeletal filaments), and
easily tunable properties in the electrical, optical and
mechanical regimes. Rational design via traditional or new
approaches, e.g., nano-casting and mesoscale chemical
lithography, can allow us to control micron- and nano-
scale features in nanowires to achieve new biointerfaces.
Both processes endogenous to the target cell and
properties of the material surface dictate the character
of these interfaces
520 In this thesis, I describe my work on the (1) synthesis
and characterization of a silicon nanowire material and
(2) use of that material in different configurations for
the optical modulation of three cellular systems. In the
first section, I discuss the synthesis of coaxial p-type/i
-type/n-type silicon nanowires (PIN-SiNWs) with enhanced
surface atomic Au, which allows for the efficient
production of photoelectrochemical currents upon 532 nm
laser illumination. Here, I also describe the adaptation
of patch clamp electrophysiology for the measurement of
photocurrents from single nanowires in an interconnect-
free configuration. In the second section, I first use
single free-standing PIN-SiNWs to optically modulate the
excitability of single primary dorsal root ganglion
neurons. I demonstrate that this neuromodulation is
occurring an atomic Au mediated photoelectrochemical
process, rather than a photothermal one. Next, I
incorporate PIN-SiNWs into a SU-8 polymeric grid structure
fabricated via photolithography and use this mesh
structure (SU-8-PIN mesh) to optically train neonatal rat
ventricular cardiomyocytes as well as adult rat hearts ex
vivo to beat at a target frequency. In these experiments,
the cardiomyocytes are cultured atop the mesh or the mesh
is stuck onto the adult hearts in the absence of a suture
or adhesive via capillary forces. A moving laser stimulus
is used to train the cardiomyocytes in both cases in order
to mimic physiological stimuli that interact with cells
not just at a single point but spatially all over the
cell. In the last case, I label PIN-SiNWs with
fluorescently conjugated streptavidin and treat primary
mouse T cells with a biotinylated anti-CD45 antibody that
allows for the generation of T cell-PIN-SiNW complexes. I
develop a method for the optical stimulation of
populations of these T cells while they are being
activated through their T cell receptors. I show that
depolarizing populations of T cells optically via a PIN-
SiNW mediated process during T cell activation dampens TCR
signaling, as demonstrated via intracellular phospho-flow
cytometry
520 In this thesis, I demonstrate non-invasive, non-genetic
optical modulation of various cellular systems using PIN-
SiNWs in a free-standing configuration that can be
dispersed in a drug-like fashion, or in a substrate
configuration as a high density mesh, or lastly as a free-
standing complex with the target cell. This work in
neurons and cardiomyocytes has implications for photo-
responsive therapeutics in the context of diseases in
excitable cell types that are characterized by aberrant
electrical activity. The work in T cells, while also
having potential for use in autoimmune therapeutics, also
helps us to understand a more fundamental question of how
membrane voltage affects T cell activation. Moreover, this
work is an example of a novel technique that can be used
to bridge electrical cellular signaling with other
signaling pathways in populations of non-excitable cells
533 Electronic reproduction.|bAnn Arbor, Mich. :|cProQuest,
|d2019
538 Mode of access: World Wide Web
650 4 Biophysics
650 4 Materials science
650 4 Biomedical engineering
655 7 Electronic books.|2local
690 0786
690 0794
690 0541
710 2 ProQuest Information and Learning Co
710 2 The University of Chicago.|bBiophysical Sciences
773 0 |tDissertation Abstracts International|g80-01B(E)
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