DSpace Collection:https://hdl.handle.net/10171/521452024-03-28T10:47:32Z2024-03-28T10:47:32ZFacet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruptionhttps://hdl.handle.net/10171/690392024-02-12T06:09:41Z2017-01-01T00:00:00ZTitle: Facet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruption
Abstract: A comprehensive understanding of the mechanisms of interaction between proteins or peptides and
nanomaterials is crucial for the development of nanomaterialbased diagnostics and therapeutics. In this work, we systematically explored the interactions between citrate-capped gold
nanoparticles (AuNPs) and islet amyloid polypeptide (IAPP),
a 37-amino acid peptide hormone co-secreted with insulin
from the pancreatic islet. We utilized diffusion-ordered
spectroscopy, isothermal titration calorimetry, localized surface
plasmon resonance spectroscopy, gel electrophoresis, atomic
force microscopy, transmission electron microscopy (TEM), and molecular dynamics (MD) simulations to systematically
elucidate the underlying mechanism of the IAPP−AuNP interactions. Because of the presence of a metal-binding sequence motif
in the hydrophilic peptide domain, IAPP strongly interacts with the Au surface in both the monomeric and fibrillar states.
Circular dichroism showed that AuNPs triggered the IAPP conformational transition from random coil to ordered structures (αhelix and β-sheet), and TEM imaging suggested the acceleration of IAPP fibrillation in the presence of AuNPs. MD simulations
revealed that the IAPP−AuNP interactions were initiated by the N-terminal domain (IAPP residues 1−19), which subsequently
induced a facet-dependent conformational change in IAPP. On a Au(111) surface, IAPP was unfolded and adsorbed directly onto
the Au surface, while for the Au(100) surface, it interacted predominantly with the citrate adlayer and retained some helical
conformation. The observed affinity of AuNPs for IAPP was further applied to reduce the level of peptide-induced lipid
membrane disruption.2017-01-01T00:00:00ZLong-Term Engraftment of Human Cardiomyocytes Combined with Biodegradable Microparticles Induces Heart Repairhttps://hdl.handle.net/10171/690382024-02-12T06:09:40Z2019-01-01T00:00:00ZTitle: Long-Term Engraftment of Human Cardiomyocytes Combined with Biodegradable Microparticles Induces Heart Repair
Abstract: Cardiomyocytes derived from human induced pluripotent stem
cells (hiPSC-CMs) are a promising cell source for cardiac repair
after myocardial infarction (MI) because they offer several
advantages such as potential to remuscularize infarcted tissue,
integration in the host myocardium, and paracrine therapeutic
effects. However, cell delivery issues have limited their potential application in clinical practice, showing poor survival and
engraftment after transplantation. In this work, we hypothesized that the combination of hiPSC-CMs with microparticles
(MPs) could enhance long-term cell survival and retention in the
heart and consequently improve cardiac repair. CMs were
obtained by differentiation of hiPSCs by small-molecule manipulation of the Wnt pathway and adhered to biomimetic
poly(lactic-co-glycolic acid) MPs covered with collagen and
poly(D-lysine). The potential of the system to support cell
survival was analyzed in vitro, demonstrating a 1.70-fold and
1.99-fold increase in cell survival after 1 and 4 days, respectively. The efficacy of the system was tested in a mouse MI
model. Interestingly, 2 months after administration, transplanted
hiPSC-CMs could be detected in the peri-infarct area. These cells
not only maintained the cardiac phenotype but also showed
in vivo maturation and signs of electrical coupling. Importantly,
cardiac function was significantly improved, which could be
attributed to a paracrine effect of cells. These findings suggest
that MPs represent an excellent platform for cell delivery in the
field of cardiac repair, which could also be translated into an
enhancement of the potential of cell-based therapies in other
medical applications.2019-01-01T00:00:00ZActivatable cell–biomaterial interfacing with photo-caged peptideshttps://hdl.handle.net/10171/690372024-02-12T06:09:39Z2019-01-01T00:00:00ZTitle: Activatable cell–biomaterial interfacing with photo-caged peptides
Abstract: Spatio-temporally tailoring cell–material interactions is essential for developing smart delivery systems and
intelligent biointerfaces. Here we report new photo-activatable cell–material interfacing systems that
trigger cellular uptake of various cargoes and cell adhesion towards surfaces. To achieve this, we
designed a novel photo-caged peptide which undergoes a structural transition from an antifouling ligand
to a cell-penetrating peptide upon photo-irradiation. When the peptide is conjugated to ligands of
interest, we demonstrate the photo-activated cellular uptake of a wide range of cargoes, including
small fluorophores, proteins, inorganic (e.g., quantum dots and gold nanostars) and organic
nanomaterials (e.g., polymeric particles), and liposomes. Using this system, we can remotely regulate
drug administration into cancer cells by functionalizing camptothecin-loaded polymeric nanoparticles
with our synthetic peptide ligands. Furthermore, we show light-controlled cell adhesion on a peptidemodified surface and 3D spatiotemporal control over cellular uptake of nanoparticles using two-photon
excitation. We anticipate that the innovative approach proposed in this work will help to establish new
stimuli-responsive delivery systems and biomaterials.2019-01-01T00:00:00ZSurface Dynamics and Ligand−Core Interactions of Quantum Sized Photoluminescent Gold Nanoclustershttps://hdl.handle.net/10171/690362024-02-12T06:09:38Z2018-01-01T00:00:00ZTitle: Surface Dynamics and Ligand−Core Interactions of Quantum Sized Photoluminescent Gold Nanoclusters
Abstract: Quantum-sized metallic clusters protected by
biological ligands represent a new class of luminescent materials;
yet the understanding of structural information and photoluminescence origin of these ultrasmall clusters remains a
challenge. Herein we systematically study the surface ligand
dynamics and ligand−metal core interactions of peptide-protected
gold nanoclusters (AuNCs) with combined experimental
characterizations and theoretical molecular simulations. We
show that the peptide sequence plays an important role in
determining the surface peptide structuring, interfacial water
dynamics and ligand−Au core interaction, which can be tailored
by controlling peptide acetylation, constituent amino acid electron donating/withdrawing capacity, aromaticity/hydrophobicity
and by adjusting environmental pH. Specifically, emission enhancement is achieved through increasing the electron density of
surface ligands in proximity to the Au core, discouraging photoinduced quenching, and by reducing the amount of surfacebound water molecules. These findings provide key design principles for understanding the surface dynamics of peptideprotected nanoparticles and maximizing the photoluminescence of metallic clusters through the exploitation of biologically
relevant ligand properties.2018-01-01T00:00:00Z