Directly Observing Micelle Fusion and Growth in Solution by Liquid-Cell Transmission Electron Microscopy

Abstract

Amphiphilic small molecules and polymers form commonplace nanoscale macromolecular compartments and bilayers, and as such are truly essential components in all cells and in many cellular processes. The nature of these architectures, including their formation, phase changes, and stimuli-response behaviors, is necessary for the most basic functions of life, and over the past half-century, these natural micellar structures have inspired a vast diversity of industrial products, from biomedicines to detergents, lubricants, and coatings. The importance of these materials and their ubiquity have made them the subject of intense investigation regarding their nanoscale dynamics with increasing interest in obtaining sufficient temporal and spatial resolution to directly observe nanoscale processes. However, the vast majority of experimental methods involve either bulk-averaging techniques including light, neutron, and X-ray scattering, or are static in nature including even the most advanced cryogenic transmission electron microscopy techniques. Here, we employ in situ liquid-cell transmission electron microscopy (LCTEM) to directly observe the evolution of individual amphiphilic block copolymer micellar nanoparticles in solution, in real time with nanometer spatial resolution. These observations, made on a proof-of-concept bioconjugate polymer amphiphile, revealed growth and evolution occurring by unimer addition processes and by particle-particle collision-and-fusion events. The experimental approach, combining direct LCTEM observation, quantitative analysis of LCTEM data, and correlated in silico simulations, provides a unique view of solvated soft matter nanoassemblies as they morph and evolve in time and space, enabling us to capture these phenomena in solution.

Intermediate states of molecular self-assembly from liquid-cell electron microscopy

“…Our different goal here is to understand time dependence. Our methods build upon liquidcell transmission electron microscopy (TEM) previously applied by others to image inorganic and metal nanoparticles (6)(7)(8)(9)(10)(11)(12), micellar and vesicle aggregates (13)(14)(15), and various methodologies (16)(17)(18). Radiation damage and electron-induced water radiolysis are normally of high concern in such experiments, but not so much in the methods implemented here, primarily because use of deuterated ("heavy") water enabled long experiments free of radiolysis-induced bubbles (19).…”

Performance of Coarse Graining in Estimating Polymer Properties: Comparison with the Atomistic Model

“…The DPD method was proven to be an effective mesoscopic simulation tool to study fluid events occurring at millisecond timescales and micrometer length scales via by tracking the motion of coarse-grained particles (composed of a group of atoms or molecules). Many researchers studied the thermodynamic and morphological behavior of polymers using the DPD method, for example, self-assembly of dendritic copolymers [25][26][27], micelle fusion or vesicle formation [28,29], and nanocomposite systems [30][31][32][33].…”

Investigating Dynamic Processes of Nanomaterials Using in Situ Liquid Phase TEM Technologies: 2014-2019

“…Although soft materials are always composed with low atomic numbers elements which usually means low contrast for TEM imaging, liquid cell TEM still shows its potential to visualize soft materials in liquid without staining. During 2014-2019, liquid cell TEM has been used to investigate micelle-micelle fusion process 48 and self-assembly 49 of amphiphilic block polymers, movements of individual water-soluble polymers 50 and proteins. 16,[51][52]…”