568 research outputs found
Multivalent "Attacker & Guard" Strategy for Targeting Surfaces with Low Receptor Density
Multivalent particles, i.e. microscopic constructs having multiple ligands,
can be used to target surfaces selectively depending on their receptor density.
Typically, there is a sharp onset of multivalent binding as the receptor
density exceeds a given threshold. However, the opposite case, selectively
binding to surfaces with a receptor density below a given threshold, is much
harder. Here, we present a simple strategy for selectively targeting a surface
with a low density of receptors, within a system also having a surface with a
higher density of the same receptors. Our strategy exploits competitive
adsorption of two species. The first species, called "guards", are
receptor-sized monovalent particles designed to occupy the high-density surface
at equilibrium, while the second multivalent "attacker" species outcompetes the
guards for binding onto the low-density surface. Surprisingly, the recipe for
attackers and guards yields more selective binding with stronger
ligand-receptor association constants, in contrast to standard multivalency. We
derive explicit expressions for the attacker and guard molecular design
parameters and concentrations, optimised within bounds of what is
experimentally accessible, thereby facilitating implementation of the proposed
approach
Simple approach for calculating the binding free energy of a multivalent particle
We present a simple yet accurate numerical approach to compute the free
energy of binding of multivalent objects on a receptor-coated surface. The
method correctly accounts for the fact that one ligand can bind to at most one
receptor. The numerical approach is based on a saddle-point approximation to
the computation of a complex residue. We compare our theory with the powerful
Valence-Limited Interaction Theory (VLIT) (J. Chem. Phys. 137, 094108(2012), J.
Chem. Phys. 138, 021102(2013)) and find excellent agreement in the regime where
that theory is expected to work. However, the present approach even works for
low receptor/ligand densities, where VLIT breaks down.Comment: 5 pages, 2 figure
Optimizing the Selectivity of Surface-Adsorbing Multivalent Polymers.
Multivalent polymers are macromolecules containing multiple chemical moieties designed to bind to complementary moieties on a target; for example, a protein with multiple ligands that have affinity for receptors on a cell surface. Though the individual ligand-receptor bonds are often weak, the combinatorial entropy associated with the different possible ligand-receptor pairs leads to a binding transition that can be very sharp with respect to control parameters, such as temperature or surface receptor concentration. We use mean-field self-consistent field theory to study the binding selectivity of multivalent polymers to receptor-coated surfaces. Polymers that have their ligands clustered into a contiguous domain, either located at the chain end or chain midsection, exhibit cooperative surface adsorption and superselectivity when the polymer concentration is low. On the other hand, when the ligands are uniformly spaced along the chain backbone, selectivity is substantially reduced due to the lack of binding cooperativity and due to crowding of the surface by the inert polymer segments in the chain backbone.This is the final version. It was first published by ACS at http://pubs.acs.org/doi/abs/10.1021/ma5014918
Harnessing entropy to enhance toughness in reversibly crosslinked polymer networks
Reversible crosslinking is a design paradigm for polymeric materials, wherein
they are microscopically reinforced with chemical species that form transient
crosslinks between the polymer chains. Besides the potential for self-healing,
recent experimental work suggests that freely diffusing reversible crosslinks
in polymer networks, such as gels, can enhance the toughness of the material
without substantial change in elasticity. This presents the opportunity for
making highly elastic materials that can be strained to a large extent before
rupturing. Here, we employ Gaussian chain theory, molecular simulation, and
polymer self-consistent field theory for networks to construct an equilibrium
picture for how reversible crosslinks can toughen a polymer network without
affecting its linear elasticity. Maximisation of polymer entropy drives the
reversible crosslinks to bind preferentially near the permanent crosslinks in
the network, leading to local molecular reinforcement without significant
alteration of the network topology. In equilibrium conditions, permanent
crosslinks share effectively the load with neighbouring reversible crosslinks,
forming multi-functional crosslink points. The network is thereby globally
toughened, while the linear elasticity is left largely unaltered. Practical
guidelines are proposed to optimise this design in experiment, along with a
discussion of key kinetic and timescale considerations
Dynamical Landau-de Gennes Theory for Electrically-Responsive Liquid Crystal Networks
Liquid crystal networks combine the orientational order of liquid crystals
with the elastic properties of polymer networks, leading to a vast application
potential in the field of responsive coatings, e.g., for haptic feedback,
self-cleaning surfaces and static and dynamic pattern formation. Recent
experimental work has further paved the way toward such applications by
realizing the fast and reversible surface modulation of a liquid crystal
network coating upon in-plane actuation with an AC electric field. Here, we
construct a Landau-type theory for electrically-responsive liquid crystal
networks and perform Molecular Dynamics simulations to explain the findings of
these experiments and inform on rational design strategies. Qualitatively, the
theory agrees with our simulations and reproduces the salient experimental
features. We also provide a set of testable predictions: the aspect ratio of
the nematogens, their initial orientational order when cross-linked into the
polymer network and the cross-linking fraction of the network all increase the
plasticization time required for the film to macroscopically deform. We
demonstrate that the dynamic response to oscillating electric fields is
characterized by two resonances, which can likewise be influenced by varying
these parameters, providing an experimental handle to fine-tune device design
Reversible microscale assembly of nanoparticles driven by the phase transition of a thermotropic liquid crystal
The arrangement of nanoscale building blocks into patterns with microscale periodicity is challenging to achieve via self-assembly processes. Here, we report on the phase-transition-driven collective assembly of gold nanoparticles in a thermotropic liquid crystal. A temperature-induced transition from the isotropic to the nematic phase under anchoring-driven planar alignment leads to the assembly of individual nanometer-sized particles into arrays of micrometer-sized agglomerates, whose size and characteristic spacing can be tuned by varying the cooling rate. Phase field simulations coupling the conserved and nonconserved order parameters exhibit a similar evolution of the morphology as the experimental observations. This fully reversible process offers control over structural order on the microscopic level and is an interesting model system for the programmable and reconfigurable patterning of nanocomposites with access to micrometer-sized periodicities
Reversible Microscale Assembly of Nanoparticles Driven by the Phase Transition of a Thermotropic Liquid Crystal
The arrangement of nanoscale building blocks into patterns with microscale periodicity is challenging to achieve via self-assembly processes. Here, we report on the phase-transition-driven collective assembly of gold nanoparticles in a thermotropic liquid crystal. A temperature-induced transition from the isotropic to the nematic phase under anchoring-driven planar alignment leads to the assembly of individual nanometer-sized particles into arrays of micrometer-sized agglomerates, whose size and characteristic spacing can be tuned by varying the cooling rate. Phase field simulations coupling the conserved and nonconserved order parameters exhibit a similar evolution of the morphology as the experimental observations. This fully reversible process offers control over structural order on the microscopic level and is an interesting model system for the programmable and reconfigurable patterning of nanocomposites with access to micrometer-sized periodicities.</p
Reversible Microscale Assembly of Nanoparticles Driven by the Phase Transition of a Thermotropic Liquid Crystal
The arrangement of nanoscale building blocks into patterns with microscale periodicity is challenging to achieve via self-assembly processes. Here, we report on the phase-transition-driven collective assembly of gold nanoparticles in a thermotropic liquid crystal. A temperature-induced transition from the isotropic to the nematic phase under anchoring-driven planar alignment leads to the assembly of individual nanometer-sized particles into arrays of micrometer-sized agglomerates, whose size and characteristic spacing can be tuned by varying the cooling rate. Phase field simulations coupling the conserved and nonconserved order parameters exhibit a similar evolution of the morphology as the experimental observations. This fully reversible process offers control over structural order on the microscopic level and is an interesting model system for the programmable and reconfigurable patterning of nanocomposites with access to micrometer-sized periodicities
Hierarchical Multivalent Effects Control Influenza Host Specificity
Understanding how emerging influenza viruses recognize host cells is critical in evaluating their zoonotic potential, pathogenicity, and transmissibility between humans. The surface of the influenza virus is covered with hemagglutinin (HA) proteins that can form multiple interactions with sialic acid-terminated glycans on the host cell surface. This multivalent binding affects the selectivity of the virus in ways that cannot be predicted from the individual receptor-ligand interactions alone. Here, we show that the intrinsic structural and energetic differences between the interactions of avian- or human-type receptors with influenza HA translate from individual site affinity and orientation through receptor length and density on the surface into virus avidity and specificity. We introduce a method to measure virus avidity using receptor density gradients. We found that influenza viruses attached stably to a surface at receptor densities that correspond to a minimum number of approximately 8 HA-glycan interactions, but more interactions were required if the receptors were short and human-type. Thus, the avidity and specificity of influenza viruses for a host cell depend not on the sialic acid linkage alone but on a combination of linkage and the length and density of receptors on the cell surface. Our findings suggest that threshold receptor densities play a key role in virus tropism, which is a predicting factor for both their virulence and zoonotic potential.Fil: Overeem, Nico J.. University of Twente; Países BajosFil: Hamming, P. H. Erik. University of Twente; Países BajosFil: Grant, Oliver C.. University of Georgia; Estados UnidosFil: Di Iorio, Daniele. University of Twente; Países BajosFil: Tieke, Malte. Utrecht University; Países BajosFil: Bertolino, María Candelaria. University of Twente; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Li, Zeshi. Utrecht University; Países BajosFil: Vos, Gaël. Utrecht University; Países BajosFil: de Vries, Robert P.. Utrecht University; Países BajosFil: Woods, Robert J.. University of Georgia; Estados UnidosFil: Tito, Nicholas B.. Electric Ant Laboratory; Países BajosFil: Boons, Geert-Jan P. H.. Utrecht University; Países BajosFil: van der Vries, Erhard. Utrecht University; Países BajosFil: Huskens, Jurriaan. University of Twente; Países Bajo
- …