Thermal motion of colloidal nanoparticles and their cohesive interactions are of fundamental importance in nanoscience but are difficult to access quantitatively, primarily due to the lack of the appropriate analytical tools to investigate the dynamics of individual particles at nanoscales. Here, we directly monitor the stochastic thermal motion and coalescence dynamics of gold nanoparticles smaller than 5 nm, using graphene liquid cell (GLC) transmission electron microscopy (TEM). We also present a novel model of nanoparticle dynamics, providing a unified, quantitative explanation of our experimental observations. The nanoparticles in a GLC exhibit non-Gaussian, diffusive motion, signifying dynamic fluctuation of the diffusion coefficient due to the dynamically heterogeneous environment surrounding nanoparticles, including organic ligands on the nanoparticle surface. Our study shows that the dynamics of nanoparticle coalescence is controlled by two elementary processes: diffusion-limited encounter complex formation and the subsequent coalescence of the encounter complex through rotational motion, where surface-passivating ligands play a critical role.

The formation mechanism of colloidal nanoparticles is complex because significant nonclassical pathways coexist with the conventional nucleation and growth processes. Particularly, the coalescence of the growing clusters determines the final morphology and crystallinity of the synthesized nanoparticles. However, the experimental investigation of the coalescence mechanism is a challenge because the process is highly kinetic and correlates with surface ligands that dynamically modify the surface energy and the interparticle interactions of nanoparticles.Here, we employ quantitative in situ TEM with multichamber graphene liquid cell to observe the coalescence processes occurring in the synthesis of gold nanoparticles in different ligand systems, thus affording us an insight into their ligand-dependent coalescence kinetics. The analyses of numerous liquid-phase TEM trajectories of the coalescence and MD simulations of the ligand shells demonstrate that enhanced ligand mobility, employing a heterogeneous ligand mixture, results in the rapid nanoparticle pairing approach and a fast post-merging structural relaxation.

structures. For example, intrinsically disordered proteins, which account for one-third of the proteins in the human proteome, do not adopt a standardized 3D structure, and their spontaneous interconversion between unfolded states is crucial in dynamic biological processes. [4] In addition, various synthetic polymers, which are highly regulated by complex molecular interactions and the resulting conformational changes, form a variety of highorder structures via the self-structuring of individual molecules. [5][6][7][8] Thus, it is important to understand the intrinsic structural diversity and dynamic behaviors of individual macromolecules at the single-chain level.Over the last few decades, the conformation and dynamics of a single chain have been widely studied both theoretically and experimentally. Theoretical and computational modeling of single-chain dynamics in ideal solutions are well established in the field of polymer physics. [9][10][11][12] Moreover, enhanced sampling simulation techniques can efficiently locate candidates for energetically stable structures and calculate the free energy differences between their distinct states. [13][14][15] Nonetheless, it is still challenging to understand realistic single-chain behaviors using computational methods, as it is not trivial to simulate ion-solute interactions, crowding, or confinement in polymer solutions. [16][17][18] Furthermore, it is not rare to find a Conformational changes in macromolecules significantly affect their functions and assembly into high-level structures. Despite advances in theoretical and experimental studies, investigations into the intrinsic conformational variations and dynamic motions of single macromolecules remain challenging. Here, liquid-phase transmission electron microscopy enables the real-time tracking of single-chain polymers. Imaging linear polymers, synthetically dendronized with conjugated aromatic groups, in organic solvent confined within graphene liquid cells, directly exhibits chain-resolved conformational dynamics of individual semiflexible polymers. These experimental and theoretical analyses reveal that the dynamic conformational transitions of the single-chain polymer originate from the degree of intrachain interactions. In situ observations also show that such dynamics of the single-chain polymer are significantly affected by environmental factors, including surfaces and interfaces.

Liquid‐phase transmission electron microscopy (TEM) offers a real‐time microscopic observation of the nanometer scale for understanding the underlying mechanisms of the growth, etching, and interactions of colloidal nanoparticles. Despite such unique capability and potential application in diverse fields of analytical chemistry, liquid‐phase TEM studies rely on information obtained from the limited number of observed events. In this work, a novel liquid cell with a large‐scale array of highly ordered nanochambers is constructed by sandwiching an anodic aluminum oxide membrane between graphene sheets. TEM analysis of colloidal gold nanoparticles dispersed in the liquid is conducted, employing the fabricated nanochamber array, to demonstrate the potential of the nanochamber array in quantitative liquid‐phase TEM. The independent TEM observations in the multiple nanochambers confirm that the monomer attachment and coalescence processes universally govern the overall growth of nanoparticles, although individual nanoparticles follow different growth trajectories.