Response of Soft Colloids and Macromolecules to Crowded Environments: Theoretical and Computational Modeling

该奖项支持理论和计算研究和教育，旨在更好地理解和促进智能材料的设计，这些材料由建筑块组成，其属性，如大小、形状和柔软度，响应和适应外部刺激的变化。有希望的构建模块类型是柔软的胶体颗粒和包含大量原子的柔性分子，称为柔性大分子，其大小可达微米-比原子大数千倍，但只能在显微镜下看到。特别令人感兴趣的是微凝胶——由链状分子的多孔弹性网络构成的微观凝胶颗粒，它们通过吸收溶剂而膨胀。颗粒的膨胀程度可以通过调节温度、酸度和溶液浓度来控制，从而产生独特的自适应特性，使微凝胶可以作为生物传感器和将药物输送到人体的载体。当在浓溶液中相互挤在一起时，柔性大分子可以改变它们的大小和形状。跨学科研究是由对材料基本结构的基本兴趣和生物医学、制药和食品工业的实际应用驱动的。虽然过去的实验和建模研究已经探索了单粒子的弹性特性和体溶液的集体行为，但一个突出的挑战是将这些材料的单粒子或微观和集体或宏观特性联系起来。具体尚未解决的问题涉及电荷在决定微凝胶膨胀中的作用以及颗粒柔软度对生物细胞中大分子拥挤的影响。在解释实验观察和设计新材料的最终目标的激励下，研究团队正在开发高效的建模方法，以实现以下几个主要目标：(1)通过模拟不同大小和柔软度的微凝胶的浓缩混合物来阐明大分子柔韧性对材料性能的影响。(2)通过模拟可变形微凝胶的拥挤溶液来分析从液体到固体的转变，并确定有利于形成结晶固体而不是玻璃固体的条件。(3)通过模拟带电荷的微凝胶浓溶液，探讨颗粒间不同作用力对软质材料热性能的影响。这项研究的一个潜在变革因素是将大分子的大小和形状波动结合起来，这在过度拥挤的环境中尤其重要，因为软颗粒会变形并相互渗透。这些目标将通过开发和应用一系列建模方法来实现，包括分子尺度的计算机模拟，以及直接将预测与实验测量进行比较。该项目更广泛的科学、教育和社会影响包括：(1)开发具有跨学科价值的新型计算机模拟算法和理论，用于柔性大分子的分散建模，这可以指导实验的解释和智能、响应材料的设计，具有潜在的应用于药物输送、生物传感器和水过滤；(2)在中小学和部落学院开展科学推广活动；(3)指导和培训学生从事计算材料研究工作。该奖项支持理论和计算研究和教育，旨在弥合我们对柔性大分子微观特性和软材料新兴宏观特性的理解。软胶体颗粒和柔性大分子，包括微凝胶和聚合物线圈，作为具有响应外部刺激变化的可调特性的智能材料的组成部分，引起了人们的强烈兴趣。特别关注的是微凝胶，这是一种天然或合成的微观凝胶颗粒，由交联聚合物的多孔弹性网络组成，被溶剂膨胀。当微凝胶分散在水中时，可以通过反离子的解离或在合成反应中从引发剂获得电荷。对溶剂分子和小离子的渗透性使得平衡粒径对渗透力、弹性力和静电力之间的竞争高度敏感。颗粒膨胀的程度可以通过调节温度、pH值、离子强度和浓度来控制，从而产生独特的适应性，使微凝胶非常适合于药物输送、化学和生物传感。在浓分散体中，微凝胶可以相互挤挤或挤挤其他大分子，或被硬纳米颗粒挤挤，导致构象变化。跨学科研究是由生物医学、制药和食品工业中有关自组装和实际应用的基本问题驱动的。微凝胶的建模大多局限于单颗粒的显式模型或多颗粒分散的粗粒度模型，而大分子拥挤的研究在很大程度上忽略了聚合物的形状。将单粒子微观结构和粒子间力与宏观性质联系起来仍然是一个突出的挑战。具体尚未解决的问题涉及静电在确定微凝胶膨胀中的作用，以及颗粒柔软性和可变形性对大分子拥挤、耗尽力和相行为的影响，包括过度拥挤分散体中结晶固体与玻璃固体的稳定性。受到这些挑战的激励，并以解释和解释实验观察结果为最终目标，促进新材料的设计，该项目正在开发高效的多尺度建模方法，以直接解决几个主要目标：(1)通过模拟具有非均匀交联密度和拥挤分散的单个颗粒，阐明微凝胶的不同内部结构和可压缩性对拥挤环境中膨胀的影响。(2)通过模拟可变形微凝胶的拥挤分散，计算结构性质和相图，分析软胶体的液固转变，以确定有利于晶体相对于玻璃固体平衡稳定性的系统参数。(3)通过模拟不对称微凝胶混合物，解释过度拥挤软胶体分散体的自愈现象以及颗粒可压缩性对体结构特性的影响。(4)通过模拟离子微凝胶的拥挤分散，确定固定电荷密度和静电相互作用在软胶体材料膨胀和热行为中的作用。(5)分析软性挤压物之间的空间作用力和静电力对聚合物线圈与纳米颗粒拥挤混合物中大分子构象的影响。(6)探索大分子拥挤对微凝胶分散体和可穿透微凝胶与硬纳米颗粒混合物的耗竭力、膨胀、结构和相行为的影响。该研究的一个潜在变革因素是将软胶体颗粒的大小和形状波动结合在一起，这在过度拥挤的环境中尤其重要，在这些环境中，体积分数超过了硬球体的紧密堆积。这些目标是通过开发、验证和应用一系列计算和理论方法来实现的，包括有效的相互作用和泊松-玻尔兹曼理论、分子动力学和蒙特卡罗模拟，以及直接将预测与实验进行比较。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

NONTECHNICAL SUMMARYThis award supports theoretical and computational research and education that is aimed to better understand and facilitate the design of smart materials composed of building blocks whose properties, such as size, shape, and softness, respond and adapt to changes in external stimuli. Promising types of building blocks are soft colloidal particles and flexible molecules containing a large number of atoms called flexible macromolecules, objects whose sizes range up to microns — thousands of times larger than an atom, yet visible only under a microscope. Of particular interest are microgels — microscopic gel particles, made of porous, elastic networks of chain-like molecules, which swell by absorbing solvent. The degree of particle swelling can be controlled by adjusting temperature, acidity, and concentration of the solution, resulting in unique, adaptive properties that equip microgels to serve as biosensors and as vehicles for delivering drugs to the body. When crowded by one another in concentrated solutions, flexible macromolecules can change their size and shape. Interdisciplinary research is driven by fundamental interest in the basic structure of materials and by practical applications in biomedical, pharmaceutical, and foods industries. While past experimental and modeling studies have explored elastic properties of single particles and collective behavior of bulk solutions, an outstanding challenge is to link single-particle or microscopic and collective or macroscopic properties of these materials. Specific unresolved issues concern the role of electric charge in determining swelling of microgels and the influence of particle softness on macromolecular crowding in biological cells.Motivated by the ultimate goal of explaining experimental observations and designing new materials, the research team is developing efficient modeling methods to achieve several major objectives: (1) Elucidate impacts of macromolecule flexibility on materials properties by modeling concentrated mixtures of microgels of different size and softness. (2) Analyze transitions from liquid to solid phases by modeling crowded solutions of deformable microgels and identifying conditions that favor formation of crystalline solids over glassy solids. (3) Explore how different forces between particles determine thermal properties of soft materials by modeling concentrated solutions of microgels with electric charge. A potentially transformative element of the research is incorporation of size and shape fluctuations of macromolecules, which are especially important in overcrowded environments, where soft particles can deform and interpenetrate. These objectives will be achieved by developing and applying an array of modeling methods, including molecular-scale computer simulations, and directly comparing predictions with experimental measurements. Broader scientific, educational, and societal impacts of this project include (1) development of novel computer simulation algorithms and theories, of interdisciplinary value, for modeling dispersions of flexible macromolecules, which can guide the interpretation of experiments and the design of smart, responsive materials, with potential applications to drug delivery, biosensors, and water filtration; (2) science outreach activities with students at K-12 schools and tribal colleges; and (3) mentoring and training of students for careers in computational materials research. TECHNICAL SUMMARYThis award supports theoretical and computational research and education that is aimed to bridge our understanding of microscopic properties of flexible macromolecules and emergent macroscopic properties of soft materials. Soft colloidal particles and flexible macromolecules, including microgels and polymer coils, have drawn intense interest as components of smart materials with tunable properties that respond to changes in external stimuli. Particular attention has been focused on microgels, that are natural or synthetic microscopic gel particles, composed of porous, elastic networks of crosslinked polymers, which are swollen by a solvent. When dispersed in water, microgels can acquire charge via dissociation of counterions or from initiators during synthesis reactions. Permeability to solvent molecules and small ions renders equilibrium particle sizes highly sensitive to competition between osmotic, elastic, and electrostatic forces. The degree of particle swelling can be controlled by adjusting temperature, pH, ionic strength, and concentration, resulting in unique, adaptive properties, and making microgels well-suited to drug delivery and chemical and biosensing. In concentrated dispersions, microgels can crowd one another or other macromolecules, or can be crowded by hard nanoparticles, resulting in conformational changes. Interdisciplinary research is driven by fundamental questions concerning self-assembly and practical applications in biomedical, pharmaceutical, and foods industries. Modeling of microgels has been mostly limited to explicit models of single particles or coarse-grained models of many-particle dispersions, while studies of macromolecular crowding have largely neglected shapes of polymers. Linking single-particle microstructure and interparticle forces with macroscopic properties remains an outstanding challenge. Specific unresolved issues concern the role of electrostatics in determining swelling of microgels and the influence of particle softness and deformability on macromolecular crowding, depletion forces, and phase behavior, including stability of crystalline vs. glassy solids in overcrowded dispersions. Motivated by these challenges, and with the ultimate goal of explaining and interpreting experimental observations to facilitate the design of new materials, this project is developing efficient, multi-scale modeling methods to directly address several major objectives: (1) Elucidate impacts of varying internal architecture and compressibility of microgels on swelling in crowded environments by modeling single particles with nonuniform crosslink density and crowded dispersions. (2) Analyze liquid-solid transitions of soft colloids by modeling crowded dispersions of deformable microgels and computing structural properties and phase diagrams to identify system parameters favoring equilibrium stability of crystals over glassy solids. (3) Explain observations of self-healing in overcrowded dispersions of soft colloids and the influence of particle compressibility on bulk structural properties by modeling asymmetric mixtures of microgels. (4) Determine the role of fixed charge density and electrostatic interactions in swelling and thermal behavior of soft colloidal materials by modeling crowded dispersions of ionic microgels. (5) Analyze impacts of steric and electrostatic forces between soft crowders on macromolecular conformations in crowded mixtures of polymer coils and nanoparticles. (6) Explore influences of macromolecular crowding on depletion forces, swelling, structure, and phase behavior in microgel dispersions and mixtures of penetrable microgels and hard nanoparticles. A potentially transformative element of the research is the incorporation of size and shape fluctuations of soft colloidal particles, which are especially important in overcrowded environments, where volume fractions exceed hard-sphere close packing. These objectives are being achieved by developing, validating, and applying an array of computational and theoretical methods, including effective interaction and Poisson-Boltzmann theories and molecular dynamics and Monte Carlo simulations, and directly comparing predictions with experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.