Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userDirect visualization of superselective colloid-surface binding mediated by multivalent interactions
94
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
Reliably distinguishing between cells based on minute differences in receptor density is crucial for cell-cell or virus-cell recognition, the initiation of signal transduction and selective targeting in directed drug delivery. Such sharp differentiation between different surfaces based on their receptor density can only be achieved by multivalent interactions. Several theoretical and experimental works have contributed to our understanding of this superselectivity, however a versatile, controlled experimental model system that allows quantitative measurements on the ligand-receptor level is still missing. Here, we present a multivalent model system based on colloidal particles equipped with surface-mobile DNA linkers that can superselectively target a surface functionalized with the complementary mobile DNA-linkers. Using a combined approach of light microscopy and Foerster Resonance Energy Transfer (FRET), we can directly observe the binding and recruitment of the ligand-receptor pairs in the contact area. We find a non-linear transition in colloid-surface binding probability with increasing ligand or receptor concentration. In addition, we observe an increased sensitivity with weaker ligand-receptor interactions and we confirm that the time-scale of binding reversibility of individual linkers has a strong influence on superselectivity. These unprecedented insights on the ligand-receptor level provide new, dynamic information into the multivalent interaction between two fluidic membranes mediated by both mobile receptors and ligands and will enable future work on the role of spatial-temporal ligand-receptor dynamics on colloid-surface binding.
rate research
Read More
Multivalent particles competing for binding on the same surface can exhibit switch-like behaviour, depending on the concentration of receptors on the surface. When the receptor concentration is low, energy dominates the free energy of binding, and particles having a small number of strongly-binding ligands preferentially bind to the surface. At higher receptor concentrations, multivalent effects become significant, and entropy dominates the binding free energy; particles having many weakly-binding ligands preferentially bind to the surface. Between these two regimes there is a switch-point, at which the surface binds the two species of particles equally strongly. We demonstrate that a simple theory can account for this switch-like behaviour and present numerical calculations that support the theoretical predictions. We argue that binding selectivity based on receptor density, rather than identity, may have practical applications.
The effective force between two parallel DNA molecules is calculated as a function of their mutual separation for different valencies of counter- and salt ions and different salt concentrations. Computer simulations of the primitive model are used and the shape of the DNA molecules is accurately modelled using different geometrical shapes. We find that multivalent ions induce a significant attraction between the DNA molecules whose strength can be tuned by the averaged valency of the ions. The physical origin of the attraction is traced back either to electrostatics or to entropic contributions. For multivalent counter- and monovalent salt ions, we find a salt-induced stabilization effect: the force is first attractive but gets repulsive for increasing salt concentration. Furthermore, we show that the multivalent-ion-induced attraction does not necessarily correlate with DNA overcharging.
Cilia and flagella often exhibit synchronized behavior; this includes phase locking, as seen in {it Chlamydomonas}, and metachronal wave formation in the respiratory cilia of higher organisms. Since the observations by Gray and Rothschild of phase synchrony of nearby swimming spermatozoa, it has been a working hypothesis that synchrony arises from hydrodynamic interactions between beating filaments. Recent work on the dynamics of physically separated pairs of flagella isolated from the multicellular alga {it Volvox} has shown that hydrodynamic coupling alone is sufficient to produce synchrony. However, the situation is more complex in unicellular organisms bearing few flagella. We show that flagella of {it Chlamydomonas} mutants deficient in filamentary connections between basal bodies display markedly different synchronization from the wild type. We perform micromanipulation on configurations of flagella and conclude that a mechanism, internal to the cell, must provide an additional flagellar coupling. In naturally occurring species with 4, 8, or even 16 flagella, we find diverse symmetries of basal body positioning and of the flagellar apparatus that are coincident with specific gaits of flagellar actuation, suggesting that it is a competition between intracellular coupling and hydrodynamic interactions that ultimately determines the precise form of flagellar coordination in unicellular algae.
Multivalent particles bind to targets via many independent ligand-receptor bonding interactions. This microscopic design spans length scales in both synthetic and biological systems. Classic examples include interactions between cells, virus binding, synthetic ligand-coated micrometer-scale vesicles or smaller nano-particles, functionalised polymers, and toxins. Equilibrium multivalent binding is a continuous yet super-selective transition with respect to the number of ligands and receptors involved in the interaction. Increasing the ligand or receptor density on the two particles leads to sharp growth in the number of bound particles at equilibrium. Here we present a theory and Monte Carlo simulations to show that applying mechanical force to multivalent particles causes their adsorption/desorption isotherm on a surface to become sharper and more selective, with respect to variation in the number of ligands and receptors on the two objects. When the force is only applied to particles bound to the surface by one or more ligands, then the transition can become infinitely sharp and first-order---a new binding regime which we term hyper-selective. Force may be imposed by, e.g. flow of solvent around the particles, a magnetic field, chemical gradients, or triggered uncoiling of inert oligomers/polymers tethered to the particles to provide a steric repulsion to the surface. This physical principle is a step towards all or nothing binding selectivity in the design of multivalent constructs.
Bacterial biofilms, surface-attached communities of cells, are in some respects similar to colloidal solids; both are densely packed with non-zero yield stresses. However, unlike non-living materials, bacteria reproduce and die, breaking mechanical equilibrium and inducing collective dynamic responses. We report experiments and theory investigating the motion of immotile Vibrio cholerae, which can kill each other and reproduce in biofilms. We vary viscosity by using bacterial variants that secrete different amounts of extracellular matrix polymers, but are otherwise identical. Unlike thermally-driven diffusion, in which diffusivity decreases with increased viscosity, we find that cellular motion mediated by death and reproduction is independent of viscosity over timescales relevant to bacterial reproduction. To understand this surprising result, we use two separate modeling approaches. First we perform explicitly mechanical simulations of one-dimensional chains of Voigt-Kelvin elements that can die and reproduce. Next, we perform an independent statistical approach, modeling Brownian motion with the classic Langevin equation under an effective temperature that depends on cellular division rate. The diffusion of cells in both approaches agrees quite well, supporting a kinetic interpretation for the effective temperature used here and developed in previous work. As the viscoelastic behavior of biofilms is believed to play a large role in their anomalous biological properties, such as antibiotic resistance, the independence of cellular diffusive motion --- important for biofilm growth and remodeling --- on viscoelastic properties likely holds ecological, medical, and industrial relevance.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
