Papers by Stefano Angioletti-Uberti
Proceedings of the National Academy of Sciences of the United States of America, Jan 11, 2023
Nanoparticles or drug carriers which can selectively bind to cells expressing receptors above a c... more Nanoparticles or drug carriers which can selectively bind to cells expressing receptors above a certain threshold surface density are very promising for targeting cells overexpressing specific receptors under pathological conditions. Simulations and theoretical studies have suggested that such selectivity can be enhanced by functionalizing nanoparticles with a bimodal polymer monolayer (BM) containing shorter ligated chains and longer inert protective chains. However, a systematic study of the effect of these parameters under tightly controlled conditions is still missing. Here, we develop well-defined and highly specific platforms mimicking particle–cell interface using surface chemistry to provide a experimental proof of such selectivity. Using surface plasmon resonance and atomic force microscopy, we report the selective adsorption of BM-functionalized nanoparticles, and especially, a significant enhanced selective behavior by using a BM with longer protective chains. Furthermore, a model is also developed to describe the repulsive contribution of the protective brush to nanoparticle adsorption. This model is combined with super-selectivity theory to support experimental findings and shows that the observed selectivity is due to the steric energy barrier which requires a high number of ligand–receptor bonds to allow nanoparticle adsorption. Finally, the results show how the relative length and molar ratio of two chains can be tuned to target a threshold surface density of receptors and thus lay the foundation for the rational design of BM-functionalized nanoparticles for selective targeting.
Frontiers of nanoscience, 2019
Abstract DNA-coated colloids (DNACCs) are one of the most exciting systems for the programmable s... more Abstract DNA-coated colloids (DNACCs) are one of the most exciting systems for the programmable self-assembly of colloidal structures. Their versatility arises naturally from the selectivity and sensitivity of DNA hybridization, which allows to finely tune the interparticle attraction to an unprecedented level. Such a possibility opens the door to assembling highly complex and stimuli-responsive structures, beyond what is achievable with other colloidal interaction. However, the link between the grafted DNA sequences and the final properties of this structures is not trivial. In particular, the physics of multivalent binding embeds DNACCs with peculiar properties which must be carefully understood to exploit the full potential of this system. To this purpose, we will describe here various theoretical and computational models developed to study DNACCs, focusing on how their main findings can be used to guide colloidal engineering.
Journal of Applied Physics, Jun 1, 2010
The public reporting burden for this collection of information is estimated to average 1 hour per... more The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.
Verhandlungen der Deutschen Physikalischen Gesellschaft, Jul 1, 2009
arXiv (Cornell University), Sep 12, 2016
Nanoparticles functionalized with multiple ligands can be programmed to bind biological targets d... more Nanoparticles functionalized with multiple ligands can be programmed to bind biological targets depending on the receptors they express, providing a general mechanism exploited in various technologies, from selective drug-delivery to biosensing. For binding to be highly selective, ligands should exclusively interact with specific targeted receptors, because formation of bonds with other, untargeted ones would lead to non-specific binding and potentially harmful behaviour. This poses a particular problem for multivalent nanoparticles, because even very weak bonds can collectively lead to strong binding. A statistical mechanical model is used here to describe how competition between different receptors together with multivalent effects can be harnessed to design ligand-functionalized nanoparticles insensitive to the presence of untargeted receptors, preventing non-specific binding.
Science Advances, Jan 24, 2020
Tight control on the selectivity of nanoparticles' interaction with biological systems is paramou... more Tight control on the selectivity of nanoparticles' interaction with biological systems is paramount for the development of targeted therapies. However, the large number of tunable parameters makes it difficult to identify optimal design "sweet spots" without guiding principles. Here, we combine superselectivity theory with soft matter physics into a unified theoretical framework and we prove its validity using blood brain barrier cells as target. We apply our approach to polymersomes functionalized with targeting ligands to identify the most selective combination of parameters in terms of particle size, brush length and density, as well as tether length, affinity, and ligand number. We show that the combination of multivalent interactions into multiplexed systems enable interaction as a function of the cell phenotype, that is, which receptors are expressed. We thus propose the design of a "bar-coding" targeting approach that can be tailor-made to unique cell populations enabling personalized therapies.
Nano Letters, May 23, 2023
Nanoscale horizons, 2023
Extracellular vesicles (EVs) are routinely released from nearly all cell types as transport vehic... more Extracellular vesicles (EVs) are routinely released from nearly all cell types as transport vehicles and for cell communication. Crucially, they contain biomolecular content for the identification of health and disease states that can be detected from readily accessible physiological fluids, including urine, plasma, or saliva. Despite their clinical utility within noninvasive diagnostic platforms such as liquid biopsies, the currently available portfolio of analytical approaches are challenged by EV heterogeneity in size and composition, as well as the complexity of native biofluids. Quartz crystal microbalance with dissipation monitoring (QCM-D) has recently emerged as a powerful alternative for the phenotypic detection of EVs, offering multiple modes of analyte discrimination by frequency and dissipation. While providing rich data for sensor development, further progress is required to reduce detection limits and fully exploit the technique's potential within biosensing. Herein, we investigate the impact of nanostructuring the sensor electrode surface for enhancing its detection capabilities. We employ self-assembly of the block copolymer polystyrene-block-poly(4-vinylpyridine) to create well defined 2D gold islands via selective impregnation of the pyridine domain with gold precursors and subsequent removal of the template. When matched to the EV length scale, we find a 4-fold improvement in sensitivity despite a 4-fold reduction in area for analyte and ligand anchoring in comparison to a flat sensor surface. Creation of tailored and confined sensing regions interspersed by non-binding silica provides optimal spatial orientation for EV capture with reduced steric effects and negative cooperativity of grafted antibodies, offering a promising route for facilitated binding and enhanced performance of sensor platforms.
Computers and Geotechnics, Oct 1, 2021
This paper outlines a framework for using molecular dynamics to simulate compression of kaolinite... more This paper outlines a framework for using molecular dynamics to simulate compression of kaolinite saturated at alkaline pH (=8) in a low (1 mM) concentration solution. The particles are modelled as flat (3D) ellipsoids and their interactions are described by a modified form of the Gay-Berne potential, calibrated against DLVO theory. The LAMMPS software was used to generate monodisperse and slightly polydisperse samples, and to simulate isotropic compression to 100 kPa. The influences of sample size and strain rate on the void ratio and the arrangement of particles within the samples were investigated via parametric studies. It is useful to consider the extent to which the system temperature (a measure of the average kinetic energy) is controlled when assessing whether the applied strain rate is appropriate. It is found that the number of particles that can be considered a representative element volume is orders of magnitude larger than the number simulated in earlier studies and that larger number of particles are required in polydisperse samples than in the monodisperse case. A comparison between the results obtained and those of published experimental studies show that the methodology proposed can deliver sensible results for the material considered.
Soft Matter, 2023
We propose a classical Density Functional Theory model to study the self-assembly of polymeric su... more We propose a classical Density Functional Theory model to study the self-assembly of polymeric surfactants on curved surfaces. We use this model to investigate the thermodynamics of phase separation of a binary mixture of size asymmetric miscible surfactants on cylindrical and spherical surfaces, and observe that phase separation driven by size alone is thermodynamically unfavorable on both cylindrical and spherical surfaces. We use the theory, supplemented by Dissipative Particle Dynamics (DPD) simulations, to predict pattern formation on a non-uniform surface with regions of positive and negative curvature. Our results suggest potential ways to couple surface topography and polymeric surfactants to design surfaces coated with non-uniform patterns.
ChemInform, Oct 10, 2014
Protein Interactions with Polymer Coatings and Biomaterials-[recent developments in analytical, b... more Protein Interactions with Polymer Coatings and Biomaterials-[recent developments in analytical, biochemical, and theoretical techniques that lead to a better understanding of polymeric biomaterials for applications as bioinert and biospecific surface coating materials in biomedical systems; 292 refs.].-(WEI, Q.; BECHERER, T.;
Angewandte Chemie, Jul 15, 2014
ABSTRACT Polymeric material coatings such as Teflon and hydrophilic polymer surfaces can prevent ... more ABSTRACT Polymeric material coatings such as Teflon and hydrophilic polymer surfaces can prevent protein adhesion to generate protein-resistant surfaces. The Review by R. Haag et al. on page 8004 ff. describes methods and recent advances in the field of protein interactions on polymeric materials. The cover picture illustrates the adsorption of proteins (egg white) to material surfaces as exemplified by the egg in the pan. (Graphic designed by Achim Wiedekind with a background picture by Ruben Haag.)
The properties of solid-liquid interfaces can be markedly altered by surfactant adsorption. Here,... more The properties of solid-liquid interfaces can be markedly altered by surfactant adsorption. Here, we use molecular dynamics simulations to study the adsorption of ionic surfactants at the interface between water and heterogeneous solid surfaces with randomly arranged hydrophilic and hydrophobic regions, which mimic the surface properties of human hair. We use the coarse-grained MARTINI model to describe both the hair surfaces and surfactant solutions. We consider negatively-charged virgin and bleached hair surface models with different grafting densities of neutral octadecyl and anionic sulfonate groups. The adsorption of cationic cetrimonium bromide (CTAB) and anionic sodium dodecyl sulfate (SDS) surfactants from water are studied above the critical micelle concentration. The simulated adsorption isotherms suggest that cationic surfactants adsorb to the surfaces via a two-stage process, initially forming monolayers and then bilayers at high concentrations, which is consistent with ...
Soft Matter
We propose a classical density functional theory model to study the self-assembly of polymeric su... more We propose a classical density functional theory model to study the self-assembly of polymeric surfactants on curved surfaces.
Biointerphases
When polymer chains are grafted to solid surfaces at sufficiently high density, they form brushes... more When polymer chains are grafted to solid surfaces at sufficiently high density, they form brushes that can modify the surface properties. In particular, polymer brushes are increasingly being used to reduce friction in water-lubricated systems close to the very low levels found in natural systems, such as synovial joints. New types of polymer brush are continually being developed to improve with lower friction and adhesion, as well as higher load-bearing capacities. To complement experimental studies, molecular simulations are increasingly being used to help to understand how polymer brushes reduce friction. In this paper, we review how molecular simulations of polymer brush friction have progressed from very simple coarse-grained models toward more detailed models that can capture the effects of brush topology and chemistry as well as electrostatic interactions for polyelectrolyte brushes. We pay particular attention to studies that have attempted to match experimental friction dat...
Proceedings of the National Academy of Sciences
Nanoparticles or drug carriers which can selectively bind to cells expressing receptors above a c... more Nanoparticles or drug carriers which can selectively bind to cells expressing receptors above a certain threshold surface density are very promising for targeting cells overexpressing specific receptors under pathological conditions. Simulations and theoretical studies have suggested that such selectivity can be enhanced by functionalizing nanoparticles with a bimodal polymer monolayer (BM) containing shorter ligated chains and longer inert protective chains. However, a systematic study of the effect of these parameters under tightly controlled conditions is still missing. Here, we develop well-defined and highly specific platforms mimicking particle–cell interface using surface chemistry to provide a experimental proof of such selectivity. Using surface plasmon resonance and atomic force microscopy, we report the selective adsorption of BM-functionalized nanoparticles, and especially, a significant enhanced selective behavior by using a BM with longer protective chains. Furthermore...
Proceedings of the National Academy of Sciences of the United States of America, Aug 31, 2021
Reliably distinguishing between cells based on minute differences in receptor density is crucial ... more 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 timescale 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.
Computers and Geotechnics
Biomacromolecules, Sep 27, 2022
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Papers by Stefano Angioletti-Uberti