4D imaging of soft matter in liquid water

Abstract

Water is a critical component for both function and structure of soft matter and it is what bestows the adjective soft. Imaging samples in liquid state is thus paramount to gathering structural and dynamical information of any soft materials. Herein we propose the use of liquid phase electron microscopy to expand ultrastructural analysis into dynamical investigations. We imaged two soft matter examples: a polymer micelle and a protein in liquid phase using transmission electron microscopy and demonstrate that the inherent Brownian motion associated with the liquid state can be exploited to gather three-dimensional information of the materials in their natural state. We call such an approach brownian tomography (BT). We combine BT with single particle analysis (Brownian particle analysis BPA) to image protein structures with a spatial resolution close that achievable using cryogenic TEM. We show that BPA allows sub-nanometer resolution of soft materials and enables to gather information on conformational changes, hydration dynamics, and the effect of thermal fluctuations.