Reconfigurability of deformable DNA origami nanoparticles on biomembranes

生物膜对活细胞是必不可少的，它们也是组织纳米颗粒在生物学和软材料中应用的宝贵界面。颗粒在膜上的黏附可以引起颗粒之间的紧急相互作用，使它们在膜上组织起来并改变其形状。以前的研究主要集中在刚性形状的纳米颗粒上。最近的进展使由DNA制成的具有精确可控形状和机械性能的可变形纳米颗粒的创造成为可能。虽然颗粒柔性在组装有组织结构中的重要性在某些领域是已知的，但还没有在纳米颗粒-膜相互作用的背景下进行探索。本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节的行为的纳米粒子奠定基础。该项目将为这项技术建立基本的理解和实用的设计原则，这项技术将开辟新的途径来探测和驱动膜的性质，并促进纳米颗粒在流体表面上的组装和动态重新配置。研究活动将与推广工作相结合，以扩大研究参与，增强科学知识，并增加大学准备。该奖项将研究可变形DNA折纸纳米颗粒与脂膜的相互作用，并在颗粒灵活性、膜变形性和由此产生的颗粒构型和自组装之间建立机械联系。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)评估膜介导的吸附纳米颗粒的变形；(3)对较高密度的纳米颗粒群体的紧急行为进行分类；以及(4)研究与膜相关的纳米颗粒在刺激下的可重构性。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本身都无法获得的见解。其基本原理是揭示生物膜和可变形的、脂质锚定的DNA折纸纳米结构的耦合行为的新理解，从而能够以可控的方式响应、组装和调节生物膜的纳米结构的预测性设计。该提案将交叉培养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，招募未被充分代表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正在崛起的高中高年级学生。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.