scholarly journals On the design of precision nanomedicines

2020 ◽  
Vol 6 (4) ◽  
pp. eaat0919 ◽  
Author(s):  
Xiaohe Tian ◽  
Stefano Angioletti-Uberti ◽  
Giuseppe Battaglia
Keyword(s):  
Particle Size ◽  
Optimal Design ◽  
Targeted Therapies ◽  
Soft Matter ◽  
Cell Phenotype ◽  
Cell Populations ◽  
Tight Control ◽  
Soft Matter Physics ◽  
Unique Cell ◽  
Sweet Spots

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.

scholarly journals On the design of precision nanomedicines

2019 ◽  
Author(s):  
Xiaohe Tian ◽  
Stefano Agioletti-Uberti ◽  
Giuseppe Battaglia
Keyword(s):  
Soft Matter ◽  
Polymer Physics ◽  
Analytical Models ◽  
Polymerization Degree ◽  
Threshold Density ◽  
Tight Control ◽  
System A ◽  
Multiple Receptors ◽  
Unique Cell ◽  
Sweet Spots

<div> <div> <p>Tight control on the selectivity of nanoparticles' interaction with biological systems is paramount for the development of targeted therapies. However, the large number of synthetically tunable parameters makes it difficult to identify optimal design ``sweet spots'' without rational guiding principles. Here we address this problem combining super-selectivity theory (SST) with analytical models from soft matter and polymer physics into a unified theoretical framework. Starting from an archetypal system, a polymersome functionalized with targeting ligands, we use our model to identify the most selective combination of parameters in terms of particle size, brush polymerization degree and grafting density, as well as tether length, binding affinity and ligands number. We further show how to combine multivalent interactions into multiplexed systems which act holistically as a function of the density of more than one receptor type, so as to achieve binding only when multiple receptors are expressed above a threshold density. We show that theory can be used to effectively fit experimental data and, hence confirming its suitability. We thus propose the design of “bar-coding" targeting approach that can be tailor-made to unique cell populations enabling personalized therapies. </p> </div> </div>

scholarly journals On the design of precision nanomedicines

2019 ◽  
Author(s):  
Xiaohe Tian ◽  
Stefano Agioletti-Uberti ◽  
Giuseppe Battaglia
Keyword(s):  
Soft Matter ◽  
Polymer Physics ◽  
Analytical Models ◽  
Polymerization Degree ◽  
Threshold Density ◽  
Tight Control ◽  
System A ◽  
Multiple Receptors ◽  
Unique Cell ◽  
Sweet Spots

<div> <div> <p>Tight control on the selectivity of nanoparticles' interaction with biological systems is paramount for the development of targeted therapies. However, the large number of synthetically tunable parameters makes it difficult to identify optimal design ``sweet spots'' without rational guiding principles. Here we address this problem combining super-selectivity theory (SST) with analytical models from soft matter and polymer physics into a unified theoretical framework. Starting from an archetypal system, a polymersome functionalized with targeting ligands, we use our model to identify the most selective combination of parameters in terms of particle size, brush polymerization degree and grafting density, as well as tether length, binding affinity and ligands number. We further show how to combine multivalent interactions into multiplexed systems which act holistically as a function of the density of more than one receptor type, so as to achieve binding only when multiple receptors are expressed above a threshold density. We show that theory can be used to effectively fit experimental data and, hence confirming its suitability. We thus propose the design of “bar-coding" targeting approach that can be tailor-made to unique cell populations enabling personalized therapies. </p> </div> </div>

Design principles for precision targeting

2017 ◽  
Author(s):  
Giuseppe Battaglia ◽  
Stefano Angioletti-Umberti
Keyword(s):  
Soft Matter ◽  
Polymer Physics ◽  
Analytical Models ◽  
Threshold Density ◽  
Tight Control ◽  
System A ◽  
Multiple Receptors ◽  
Unique Cell ◽  
Polymer Stabilized ◽  
Sweet Spots

<div> <div> <div> <p>Tight control on the selectivity of nanoparticles’ interaction with biological systems is paramount for the development of targeted therapies. However, the large number of synthetically tuneable parameters makes it difficult to identify optimal design “sweet spots” without rational guiding principles. Here we address this problem combining super-selectivity theory (SST) with analytical models from soft matter and polymer physics into a unified theoretical framework. Starting from an archetypal system, a polymer-stabilized nanoparticle function- alised with targeting ligands, we use our model to identify the most selective combination of parameters in terms of particle size, brush polymerization degree and grafting density, as well as tether length, binding affinity and ligands number. We further show how to combine mul- tivalent interactions into multiplexed systems which act holistically as a function of the den- sity of more than one receptor type, so as to achieve binding only when multiple receptors are expressed above a threshold density. We thus propose the design of ”bar-coding” targeting approach that can be tailor-made to unique cell populations enabling personalized therapies. </p> </div> </div> </div>

Design principles for precision targeting

2018 ◽  
Author(s):  
Giuseppe Battaglia ◽  
Stefano Agioletti-Uberti
Keyword(s):  
Particle Size ◽  
Soft Matter ◽  
Polymer Physics ◽  
Analytical Models ◽  
Polymerization Degree ◽  
Tight Control ◽  
System A ◽  
Grafting Density ◽  
Polymer Stabilized ◽  
Sweet Spots

<div> <div> <div> <p>Tight control on the selectivity of nanoparticles’ interaction with biological systems is paramount for the development of targeted therapies. However, the large number of synthetically tuneable parameters makes it difficult to identify optimal design “sweet spots” without rational guiding principles. Here we address this problem combining super-selectivity theory (SST) with analytical models from soft matter and polymer physics into a unified theoretical framework. Starting from an archetypal system, a polymer-stabilized nanoparticle function- alised with targeting ligands, we use our model to identify the most selective combination of parameters in terms of particle size, brush polymerization degree and grafting density, as well as tether length, binding affinity and ligands number. </p> </div> </div> </div>

scholarly journals On the design of precision nanomedicines

2019 ◽  
Author(s):  
Xiaohe Tian ◽  
Stefano Agioletti-Uberti ◽  
Giuseppe Battaglia
Keyword(s):  
Soft Matter ◽  
Polymer Physics ◽  
Analytical Models ◽  
Polymerization Degree ◽  
Threshold Density ◽  
Tight Control ◽  
System A ◽  
Multiple Receptors ◽  
Unique Cell ◽  
Sweet Spots

<div> <div> <p>Tight control on the selectivity of nanoparticles' interaction with biological systems is paramount for the development of targeted therapies. However, the large number of synthetically tunable parameters makes it difficult to identify optimal design ``sweet spots'' without rational guiding principles. Here we address this problem combining super-selectivity theory (SST) with analytical models from soft matter and polymer physics into a unified theoretical framework. Starting from an archetypal system, a polymersome functionalized with targeting ligands, we use our model to identify the most selective combination of parameters in terms of particle size, brush polymerization degree and grafting density, as well as tether length, binding affinity and ligands number. We further show how to combine multivalent interactions into multiplexed systems which act holistically as a function of the density of more than one receptor type, so as to achieve binding only when multiple receptors are expressed above a threshold density. We show that theory can be used to effectively fit experimental data and, hence confirming its suitability. We thus propose the design of “bar-coding" targeting approach that can be tailor-made to unique cell populations enabling personalized therapies. </p> </div> </div>

Introduction to molecular simulations in soft matter

2017 ◽  
Author(s):  
J.-L. Barrat ◽  
J. J. de Pablo
Keyword(s):  
Phase Space ◽  
Numerical Methods ◽  
Theoretical Basis ◽  
Soft Matter ◽  
Relevant Literature ◽  
Coarse Grained ◽  
Soft Interfaces ◽  
Molecular Scale ◽  
Soft Matter Physics ◽  
The Continuum

We describe the main features of the coarse-grained models that are typically useful in modelling soft interfaces, from force fields to the continuum descriptions involving density fields. We explain the theoretical basis of the main numerical methods that are used to explore the phase space associated with these models. Finally, three recent examples, illustrating the spirit in which relatively simple simulations can contribute to solving pending problems in soft matter physics, are briefly described. Clearly, a short series of lectures can offer, at best, a biased and restricted view of the available approaches. Our aim here will be to provide the reader with such an overview, with a focus on methods and descriptions that ‘bridge the scale’ between the molecular scale and the continuum or quasi-continuum one. The objective to present a guide to the relevant literature—which has now to a large extent appeared in the form of textbooks.

Application of video microscopy in experimental soft matter physics

2018 ◽  
Vol 32 (18) ◽  
pp. 1840012
Author(s):  
Hao Feng ◽  
Huaguang Wang ◽  
Zexin Zhang
Keyword(s):  
Video Processing ◽  
Soft Matter ◽  
Colloidal Suspensions ◽  
Real Space ◽  
Video Microscopy ◽  
Quantitative Image ◽  
Soft Matter Physics ◽  
Microscopic World ◽  
The One ◽  
Microscopic Measurement

Combining precise microscopic measurement with quantitative image analysis, video microscopy has become one of the most important, real-space experiment techniques to study the microscopic properties of soft matter systems. On the one hand, it provides a basic tool to observe and record the microscopic world. On the other hand, it offers a powerful experiment method to study the underlying physics of the microscopic world. In this paper, we review the development of the video microscopy, introduce the corresponding hardware and video processing software, and summarize the typical applications and recent progresses of video microscopy in colloidal suspensions. The future of the video microscopy in the soft condensed matter physics and interdisciplinary research is discussed.

scholarly journals Recent Advances in Conservation–Dissipation Formalism for Irreversible Processes

Entropy ◽  
2021 ◽  
Vol 23 (11) ◽  
pp. 1447
Author(s):  
Liangrong Peng ◽  
Liu Hong
Keyword(s):  
Soft Matter ◽  
Irreversible Processes ◽  
Recent Advances ◽  
Classical Models ◽  
Fourier Heat Conduction ◽  
Soft Matter Physics ◽  
Novel Applications ◽  
Fokker Planck Equations ◽  
Mathematical Foundations ◽  
Well Posed

The main purpose of this review is to summarize the recent advances of the Conservation–Dissipation Formalism (CDF), a new way for constructing both thermodynamically compatible and mathematically stable and well-posed models for irreversible processes. The contents include but are not restricted to the CDF’s physical motivations, mathematical foundations, formulations of several classical models in mathematical physics from master equations and Fokker–Planck equations to Boltzmann equations and quasi-linear Maxwell equations, as well as novel applications in the fields of non-Fourier heat conduction, non-Newtonian viscoelastic fluids, wave propagation/transportation in geophysics and neural science, soft matter physics, etc. Connections with other popular theories in the field of non-equilibrium thermodynamics are examined too.

scholarly journals Modeling cellular crosstalk and organotypic vasculature development with human iPSC-derived endothelial cells and cardiomyocytes

2020 ◽  
Author(s):  
Emmi Helle ◽  
Minna Ampuja ◽  
Alexandra Dainis ◽  
Laura Antola ◽  
Elina Temmes ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Tissue Growth ◽  
Cell Phenotype ◽  
Cell Populations ◽  
Pump System ◽  
Single Cell Rna Sequencing

AbstractRationaleCell-cell interactions are crucial for the development and function of the organs. Endothelial cells act as essential regulators of tissue growth and regeneration. In the heart, endothelial cells engage in delicate bidirectional communication with cardiomyocytes. The mechanisms and mediators of this crosstalk are still poorly known. Furthermore, endothelial cells in vivo are exposed to blood flow and their phenotype is greatly affected by shear stress.ObjectiveWe aimed to elucidate how cardiomyocytes regulate the development of organotypic phenotype in endothelial cells. In addition, the effects of flow-induced shear stress on endothelial cell phenotype were studied.Methods and resultsHuman induced pluripotent stem cell (hiPSC) -derived cardiomyocytes and endothelial cells were grown either as a monoculture or as a coculture. hiPS-endothelial cells were exposed to flow using the Ibidi-pump system. Single-cell RNA sequencing was performed to define cell populations and to uncover the effects on their transcriptomic phenotypes. The hiPS-cardiomyocyte differentiation resulted in two distinct populations; atrial and ventricular. Coculture had a more pronounced effect on hiPS-endothelial cells compared to hiPS-cardiomyocytes. Coculture increased hiPS-endothelial cell expression of transcripts related to vascular development and maturation, cardiac development, and the expression of cardiac endothelial cell -specific genes. Exposure to flow significantly reprogrammed the hiPS-endothelial cell transcriptome, and surprisingly, promoted the appearance of both venous and arterial clusters.ConclusionsSingle-cell RNA sequencing revealed distinct atrial and ventricular cell populations in hiPS-cardiomyocytes, and arterial and venous-like cell populations in flow exposed hiPS-endothelial cells. hiPS-endothelial cells acquired cardiac endothelial cell identity in coculture. Our study demonstrated that hiPS-cardiomoycytes and hiPS-endothelial cells readily adapt to coculture and flow in a consistent and relevant manner, indicating that the methods used represent improved physiological cell culturing conditions that potentially are more relevant in disease modelling. In addition, novel cardiomyocyte-endothelial cell crosstalk mediators were revealed.

scholarly journals Paraspeckles are constructed as block copolymer micelles through microphase separation

2020 ◽  
Author(s):  
Tomohiro Yamazaki ◽  
Tetsuya Yamamoto ◽  
Hyura Yoshino ◽  
Sylvie Souquere ◽  
Shinichi Nakagawa ◽  
...  
Keyword(s):  
Block Copolymer ◽  
Soft Matter ◽  
Microphase Separation ◽  
Theoretical Framework ◽  
Internal Organization ◽  
Ribonucleoprotein Complexes ◽  
Block Copolymer Micelles ◽  
Copolymer Micelles ◽  
Rna Domains ◽  
Soft Matter Physics

SummaryParaspeckles are constructed by NEAT1_2 architectural long noncoding RNAs and possess characteristic cylindrical shapes with highly ordered internal organization, distinct from typical liquid–liquid phase-separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. We then applied a theoretical framework using soft matter physics to understand the principles that determine the NEAT1_2 organization, shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through microphase separation. This work provides an experimentally-based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA-scaffolding microphase-separated condensates in cells.

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