Enzyme-responsive micelles have great potential as drug delivery platforms due to the high selectivity of the activating enzymes. Here we report a highly modular design for the efficient and simple synthesis of amphiphilic block copolymers based on a linear hydrophilic polyethyleneglycol (PEG) and an enzyme-responsive hydrophobic dendron. These amphiphilic hybrids self-assemble in water into micellar nanocontainers that can disassemble and release encapsulated molecular cargo upon enzymatic activation. The utilization of monodisperse dendrons as the stimuli-responsive block enabled a detailed kinetic study of the molecular mechanism of the enzymatically triggered disassembly. The modularity of these PEG-dendron hybrids allows control over the disassembly rate of the formed micelles by simply tuning the PEG length. Such smart amphiphilic hybrids could potentially be applied for the fabrication of nanocarriers with adjustable release rates for delivery applications.
Neurofilaments (NF)--the principal cytoskeletal constituent of myelinated axons in vertebrates--consist of three molecular-weight subunit proteins NF-L (low), NF-M (medium) and NF-H (high), assembled to form mature filaments with protruding unstructured C-terminus side arms. Liquid-crystal gel networks of side-arm-mediated neurofilament assemblies have a key role in the mechanical stability of neuronal processes. Disruptions of the neurofilament network, owing to neurofilament over-accumulation or incorrect side-arm interactions, are a hallmark of motor-neuron diseases including amyotrophic lateral sclerosis. Using synchrotron X-ray scattering, we report on a direct measurement of forces in reconstituted neurofilament gels under osmotic pressure (P). With increasing pressure near physiological salt and average phosphorylation conditions, NF-LMH, comprising the three subunits near in vivo composition, or NF-LH gels, undergo for P > P(c) approximately 10 kPa, an abrupt non-reversible gel-expanded to gel-condensed transition. The transition indicates side-arm-mediated attractions between neurofilaments consistent with an electrostatic model of interpenetrating chains. In contrast, NF-LM gels remain in a collapsed state for P < P(c) and transition to the gel-condensed state at P > P(c). These findings, which delineate the distinct roles of NF-M and NF-H in regulating neurofilament interactions, shed light on possible mechanisms for disruptions of optimal mechanical network properties.
A simple hybrid design has been developed to produce practically scatterless aperture slits for small‐angle X‐ray scattering and high‐resolution X‐ray diffraction. The hybrid slit consists of a rectangular single‐crystal substrate (e.g. Si or Ge) bonded to a high‐density metal base with a large taper angle (> 10°). The beam‐defining single‐crystal tip is oriented far from any Bragg peak position with respect to the incident beam and hence produces none of the slit scattering commonly associated with conventional metal slits. It has been demonstrated that the incorporation of the scatterless slits leads to a much simplified design in small‐angle X‐ray scattering instruments employing only one or two apertures, with dramatically increased intensity (a threefold increase observed in the test setup) and improved low‐angle resolution.
Most
natural biomolecules may exist in either of two enantiomeric
forms. Although in nature, amino acid biopolymers are characterized
by l-type homochirality, incorporation of d-amino
acids in the design of self-assembling peptide motifs has been shown
to significantly alter enzyme stability, conformation, self-assembly
behavior, cytotoxicity, and even therapeutic activity. However, while
functional metabolite assemblies are ubiquitous throughout nature
and play numerous important roles including physiological, structural,
or catalytic functions, the effect of chirality on the self-assembly
nature and function of single amino acids is not yet explored. Herein,
we investigated the self-assembly mechanism of amyloid-like structure
formation by two aromatic amino acids, phenylalanine (Phe) and tryptophan
(Trp), both previously found as extremely important for the nucleation
and self-assembly of aggregation-prone peptide regions into functional
structures. Employing d-enantiomers, we demonstrate the critical
role that amino acid chirality plays in their self-assembly process.
The kinetics and morphology of pure enantiomers is completely altered
upon their coassembly, allowing to fabricate different nanostructures
that are mechanically more robust. Using diverse experimental techniques,
we reveal the different molecular arrangement and self-assembly mechanism
of the dl-racemic mixtures that resulted in the formation
of advanced supramolecular materials. This study provides a simple
yet sophisticated engineering model for the fabrication of attractive
materials with bionanotechnological applications.
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