Videbæk Thomas E, Hayakawa Daichi, Hagan Michael F, Grason Gregory M, Fraden Seth, Rogers W Benjamin
Martin A. Fisher School of Physics, Brandeis University, Waltham, MA 02453.
Department of Polymer Science and Engineering, University of Massachusetts, Amherst, MA 01003.
Proc Natl Acad Sci U S A. 2025 Sep 16;122(37):e2500716122. doi: 10.1073/pnas.2500716122. Epub 2025 Sep 9.
Programmable self-assembly has recently enabled the creation of complex structures through precise control of the interparticle interactions and the particle geometries. Targeting ever more structurally complex, dynamic, and functional assemblies necessitates going beyond the design of the structure itself, to the measurement and control of the local flexibility of the intersubunit connections and its impact on the collective mechanics of the entire assembly. In this study, we demonstrate a method to infer the mechanical properties of multisubunit assemblies using cryogenic electron microscopy (cryo-EM) and RELION's multi-body refinement. Specifically, we analyze the fluctuations of pairs of DNA-origami subunits that self-assemble into tubules. By measuring the fluctuations of dimers using cryo-EM, we extract mechanical properties such as the bending modulus and interparticle spring constant. These properties are then applied to elastic models to predict assembly outcomes, which align well with experimental observations. This approach not only provides a deeper understanding of nanoparticle mechanics but also opens pathways to refining subunit designs to achieve precise assembly behavior. This methodology could have broader applications in the study of nanomaterials, including protein assemblies, where understanding the interplay of mechanical properties and subunit geometry is essential for controlling complex self-assembled structures.
可编程自组装最近通过对粒子间相互作用和粒子几何形状的精确控制，实现了复杂结构的创建。针对结构越来越复杂、动态且功能化的组件，需要超越结构本身的设计，深入到亚基间连接的局部柔韧性的测量与控制，以及其对整个组件集体力学的影响。在本研究中，我们展示了一种使用低温电子显微镜（cryo-EM）和RELION的多体精修来推断多亚基组件力学性质的方法。具体而言，我们分析了自组装成微管的DNA折纸亚基对的波动情况。通过使用低温电子显微镜测量二聚体的波动，我们提取了诸如弯曲模量和粒子间弹簧常数等力学性质。然后将这些性质应用于弹性模型以预测组装结果，这些结果与实验观察结果吻合良好。这种方法不仅能更深入地理解纳米粒子力学，还为优化亚基设计以实现精确的组装行为开辟了道路。该方法在纳米材料研究中可能有更广泛的应用，包括蛋白质组装，其中理解力学性质和亚基几何形状的相互作用对于控制复杂的自组装结构至关重要。
