Reconfigurability of deformable DNA origami nanoparticles on biomembranes

生物膜对活细胞至关重要，它们也是组织纳米颗粒的有价值的界面，用于生物学和软材料的应用。颗粒粘附在膜上可以引起颗粒之间的紧急相互作用，使它们在膜上组织并改变其形状。以前的研究主要集中在具有刚性形状的纳米颗粒上。最近的进展使人们能够制造出由DNA制成的可变形纳米颗粒，这种纳米颗粒具有精确可控的形状和机械性能。虽然粒子柔韧性在有组织结构组装中的重要性在某些领域是已知的，但在纳米粒子-膜相互作用的背景下还没有被探索过。这个项目是对可变形和可重构纳米颗粒在生物膜上的吸附和组织的定量研究。这将为合理设计具有比刚性粒子更复杂和可调行为的纳米粒子奠定基础。该项目将为一项技术建立基本的理解和实用的设计原则，该技术将为探测和驱动膜的特性开辟新的途径，并促进纳米颗粒在流体表面的组装和动态可重构性。研究活动将与外展工作相结合，以扩大研究参与，提高科学知识，并提高大学准备。该奖项将研究可变形的DNA折纸纳米粒子与脂质膜的相互作用，并在粒子的柔韧性、膜的可变形性以及粒子的最终构型和自组装之间建立机制联系。具体目标包括(1)定量表征可变形纳米颗粒在膜上的吸附；(2)评估吸附纳米颗粒的膜介导变形；(3)对高密度下纳米粒子群体的涌现行为进行分类；(4)研究刺激触发膜相关纳米颗粒的可重构性。这项研究将利用互补的计算和实验方法来提供任何一种方法都无法单独获得的见解。其基本原理是揭示对生物膜和可变形的、脂质锚定的DNA折纸纳米结构的耦合行为的新理解，从而使纳米结构的预测设计能够以可控的方式响应、组装和调节生物膜。该提案将交叉培训研究生和本科生研究人员，鼓励转学前的社区大学生从事研究，招募代表性不足的群体为研究项目做出贡献，并通过实践项目和研究指导来教育即将升入高中的高年级学生。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。

Biomembranes are essential to living cells, and they also serve as a valuable interface for organizing nanoparticles for applications in biology and soft materials. Adhesion of particles onto a membrane can give rise to emergent interactions between particles that cause them to organize on the membrane and transform its shape. Previous research has focused predominantly on nanoparticles with rigid shapes. Recent advances enable the creation of deformable nanoparticles, made from DNA, that have precisely controllable shapes and mechanical properties. While the importance of particle flexibility in the assembly of organized structures is known in some fields, it has not been explored in the context of nanoparticle-membrane interactions. This project is a quantitative study of the adsorption and organization of deformable and reconfigurable nanoparticles on biomembranes. It will lay the groundwork for the rational design of nanoparticles with more complex and tunable behaviors than is possible with rigid particles. This project will establish fundamental understanding and practical design principles for a technology that will open new avenues to probe and actuate properties of membranes and to facilitate the assembly and dynamic reconfigurability of nanoparticles on fluid surfaces. Research activities will be integrated with outreach efforts to broaden research participation, enhance scientific knowledge, and increase college preparedness.This award will investigate interactions of deformable DNA origami nanoparticles with lipid membranes and establish a mechanistic link between particle flexibility, membrane deformability, and the resulting configurations and self-assembly of the particles. Specific objectives include (1) quantitatively characterizing adsorption of deformable nanoparticles onto membranes; (2) assessing membrane-mediated deformations of adsorbed nanoparticles; (3) classifying emergent behaviors of populations of nanoparticles at higher densities; and (4) studying stimuli-triggered reconfigurability of membrane-associated nanoparticles. The study will leverage complementary computational and experimental methods to provide insight inaccessible to either approach on its own. The rationale is to reveal new understanding of the coupled behaviors of biomembranes and deformable, lipid-anchored DNA origami nanostructures, thus enabling predictive design of nanostructures that respond to, assemble on, and modulate biomembranes in controllable manners. The proposal will cross-train graduate and undergraduate researchers, encourage pre-transfer community college students to engage in research, recruit underrepresented groups to contribute to the research project, and educate rising high school seniors through hands-on projects and research mentorship.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.