Significance A basic requirement in biomedical research is the ability to specifically target cells and tissues. Targeting typically relies on specific binding of a “ligand” tailor-made probe “receptor” desired cell/tissue. Conventional probes efficiently distinguish biological entity displaying receptor from others that do not, but exhibit limited selectivity when entities be distinguished display given at different densities. Multivalent bind several receptors simultaneously potentially...

Despite their importance for material and life sciences, multivalent interactions between polymers surfaces remain poorly understood. Combining recent achievements of synthetic chemistry surface characterization, we have developed a well-defined highly specific model system based on host/guest interactions. We use this to study the binding hyaluronic acid functionalized with host molecules tunable displaying different densities guest molecules. Remarkably, find that density bound polymer...

ConspectusMultivalent interactions are common in biological systems and also widely deployed for targeting applications biomedicine. A unique feature of multivalent binding is "superselectivity". Superselectivity refers to the sharp discrimination surfaces (e.g., on cells or cell compartments) by their comparative surface densities a given receptor. This different from conventional "type" selectivity, which discriminates distinct receptor types. In broader definition, probe superselective if...

Significance A key challenge in biomedical research is the ability to specifically target cells and tissues. Targeting typically relies on identifying a suitable marker, e.g., highly expressed receptor, choosing ligand that strongly binds marker. However, this procedure fails when marker unique targeted cannot be identified, notably many forms of cancer. We show properly designed multivalent targeting multiple cognate receptor types results specificity toward chosen density profile, thus...

During the last decade coarse-grained nucleotide models have emerged that allow us to study DNA and RNA on unprecedented time length scales. Among them is oxDNA, a coarse-grained, sequence-specific model captures hybridisation transition of many structural properties single- double-stranded DNA. oxDNA was previously only available as standalone software, but has now been implemented into popular LAMMPS molecular dynamics code. This article describes new implementation analyses its parallel...

Nanoparticles in solution acquire charge through the dissociation or association of surface groups. Thus, a proper description their electrostatic interactions requires use charge-regulating boundary conditions rather than commonly employed constant-charge approximation. We implement hybrid Monte Carlo/molecular dynamics scheme that dynamically adjusts charges individual groups objects while evolving trajectories. Charge regulation effects are shown to qualitatively change self-assembled...

The net charge of solvated entities, ranging from polyelectrolytes and biomolecules to charged nanoparticles membranes, depends on the local dissociation equilibrium individual ionizable groups. Incorporation this phenomenon, regulation (CR), in theoretical computational models requires dynamic, configuration-dependent recalculation surface charges is therefore typically approximated by assuming constant particles. Various methods exist that address this. We present an alternative,...

The interaction between a biological membrane and its environment is complex process, as it involves multivalent binding ligand/receptor pairs, which can self-organize in patches. Any description of the specific biomolecules to membranes must account for key characteristics binding, namely, unique ability discriminate sharply high low receptor densities (superselectivity), but also effect lateral mobility membrane-bound receptors cluster upon binding. Here we present an experimental model...

Lipid nanoparticles (LNP) have emerged as pivotal delivery vehicles for RNA therapeutics. Previous research and development usually assumed that LNPs are homogeneous in population, loading density, composition. Such perspectives difficult to examine due the lack of suitable tools characterize these physicochemical properties at single-nanoparticle level. Here, we report an integrated spectroscopy-chromatography approach a generalizable strategy dissect complexities multicomponent LNP...

We investigate the flow of an electrolyte through a rigid nanochannel decorated with surface charge pattern. Employing lattice Boltzmann and dissipative particle dynamics methods, as well analytical theory, we show that electrohydrodynamic coupling leads to two distinct regimes. The accompanying discontinuous transition between slow, ionic, fast, Poiseuille flows is observed at intermediate ion concentrations, channel widths, electrostatic strengths. These findings indicate routes design...

The immune system exploits a wide range of strategies to combine sensitivity with selectivity for optimal response. We propose generic physical mechanism that allows tuning the location and steepness response threshold cellular processes activated by multivalent binding. is based on possibility modulate attraction between membrane receptors. use theory simulations show how interreceptor can enhance or suppress binding ligand-coated particles surfaces. changes in less than thermal energy k B...

Lévy walks as a random search strategy have recently attracted lot of attention, and been described in many animal species. However, very little is known about one the most important issues, namely how are generated by biological organisms. We study model chemotaxis signaling pathway E. coli, demonstrate that stochastic fluctuations specific design concert enable generation walks. show result from superposition an ensemble exponential distributions, which occurs due to shifts internal enzyme...

We present an integrated theory of molecular imprinting and derive a set general design principles for molecularly imprinted polymers.

Moieties that compete with multivalent interactions or act as cofactors are common in living systems, but their effect on binding remains poorly understood. We derive a theoretical model shows how the superselectivity of is modulated by presence competitors. find role these participating moieties can be fully captured simple rescaling affinity constant individual ligand–receptor bonds. Theoretical predictions supported experimental data membrane repair protein annexin A5 to anionic lipid...

The organization of nano-particles inside grafted polymer layers is governed by the interplay polymer-induced entropic interactions and action externally applied fields. Earlier work had shown that strong external forces can drive formation colloidal structures in brushes. Here we show fields are not essential to obtain such patterns: report Monte Carlo Molecular dynamics simulations demonstrate ordered be achieved compressing a `sandwich' two layers, or squeezing coated nanotube, with...

Double-stranded RNA (dsRNA) induces production of pro-inflammatory cytokines in normal human epidermal keratinocytes (NHEK) by specific binding to endosomal Toll-like receptor-3 (TLR3). Recently, it has been shown that hyperactivation TLR3 psoriatic dsRNA can occur the presence antimicrobial peptide (AMP) LL37. Here, we combine synchrotron X-ray scattering, microscopy, computer simulations, and measurements NHEK cytokine elucidate a previously unanticipated form molecular pattern...

We develop a computational method based on Dissipative Particle Dynamics (DPD) that introduces solvent hydrodynamic interactions to coarse-grained models of solutes, such as ions, molecules, or polymers. DPD-solvent (DPDS) is fully off-lattice allows straightforward incorporation hydrodynamics at desired viscosity, compressibility, and solute diffusivity with any particle-based model. Solutes interact the only through DPD thermostat, which ensures equilibrium properties system are not...

Selective targeting of membranes with a specific receptor profile is an ongoing challenge in targeted drug delivery. We investigate the adsorption copolymers on multicomponent receptor-covered surface using grand-canonical Monte Carlo simulations and demonstrate that polymers can be designed to target particular density profile. To achieve this, ligand should match profile, ligand–receptor affinity inversely proportional While same obtained multivalent nanoparticles, entropic effects due...

Organic crystals formed by small molecules can be highly functional but are often brittle or insoluble structures with limited possibilities for use processing from a liquid phase. A possible solution is the nanoscale integration of polymers into organic without sacrificing long-range order and therefore function. This enables to benefit advantageous mechanical chemical properties polymeric component. We report here on strategy in which cocrystallize side chains chemically disordered create...

Biological membranes typically contain a large number of different components dispersed in small concentrations the main membrane phase, including proteins, sugars, and lipids varying geometrical properties. Most these do not bind cargo. Here, we show that such "inert" can be crucial for precise control cross-membrane trafficking. Using statistical mechanics model molecular dynamics simulations, demonstrate presence inert isotropic curvatures dramatically influences cargo endocytosis, even...

We investigate the collapse and expansion dynamics of a linear polyelectrolyte (PE) with hydrodynamic interactions. Using dissipative particle bead–spring PE model, long-range electrostatics, explicit ions, we examine how timescales tcol texp depend on chain length N obtain scaling relationships ∼ Nα Nβ. For neutral polymers, derive values α = 0.94 ± 0.01 β 1.97 0.10. Interestingly, introduction electrostatic interaction markedly shifts to ≈ 1.4 0.1 for salt concentrations within c 10−4 10−2...

Although the free energy of a genome packing into virus is dominated by DNA-DNA interactions, ordering DNA inside capsid elasticity driven, suggesting general solutions with organized spool-like domains. Using analytical calculations and computer simulations long elastic filament confined to spherical container, we show that ground state not single spool as assumed hitherto, but an mosaic multiple homogeneously ordered At low densities, observe concentric spools, while at higher other...