Liposome Cryo-EM
Liposome Cryo-EM refers to a technique for conducting in situ, high-resolution imaging of synthetically engineered liposomes using cryo-electron microscopy. This method combines the high precision of advanced electron microscopy with the biological relevance of liposome-based model systems, enabling structural and physicochemical characterization of liposomes under near-native conditions. These analyses include their ultrastructure, physical properties, and interactions with therapeutic molecules such as drugs or proteins. As a widely used drug delivery vehicle, liposomes have extensive applications in small molecule transport, vaccine formulations, and nucleic acid-based therapeutics. Liposome Cryo-EM enables researchers to directly visualize liposome morphology, lamellarity, size distribution, and internal architecture at the nanoscale, thereby providing essential structural insights and quantitative data for the design and optimization of delivery systems. This technique has become increasingly central to areas such as nanomedicine development, biomembrane modeling, and validation of delivery platforms. In drug development, time-resolved Cryo-EM allows for dynamic monitoring of liposome structural evolution under varying conditions—such as pH fluctuations, enzymatic activity, or ionic strength—revealing events like vesicle rupture, membrane fusion, and morphological transformations. These dynamic structural insights are critical for understanding delivery mechanisms, regulating drug release, and enhancing in vivo stability. By uncovering these nanoscale transformation pathways, Liposome Cryo-EM facilitates a shift from experience-driven to structure-guided carrier design, significantly enhancing the predictability and controllability of liposomal drug delivery systems. Furthermore, liposomes are frequently employed as biomimetic models of cellular and endomembrane systems. Cryo-EM enables in situ observation of lipid bilayer–membrane protein interactions, revealing key features such as protein-induced conformational changes, localization patterns, and their role in modulating membrane curvature.
The working principle of Liposome Cryo-EM involves rapidly vitrifying the liposome sample by plunging it into liquid nitrogen-cooled cryogens without any chemical fixation or staining. This process embeds the specimen in amorphous ice, preserving its native ultrastructure. The vitrified sample is then imaged at cryogenic temperatures using transmission electron microscopy (TEM), wherein an electron beam scans the sample and the imaging system captures two-dimensional projection images. Computational reconstruction methods are subsequently employed to derive three-dimensional structural information. Compared to conventional TEM, Liposome Cryo-EM avoids sample deformation and artifacts induced by dehydration and staining, providing a faithful representation of liposomes in aqueous environments. This approach is particularly suited for resolving hydrated membrane features, bilayer organization, and local heterogeneities. Consequently, Liposome Cryo-EM offers not only high spatial resolution but also strong biological relevance, making it an indispensable tool for the structural characterization of liposomes.
The advantages of Liposome Cryo-EM are evident across several dimensions. First, in particle size analysis, this technique allows precise measurement of the size and shape distribution of individual liposomes, and is especially adept at capturing complex features such as multilamellar vesicles, membrane fusion events, and abnormal morphologies. Second, in resolving layered structures, Liposome Cryo-EM enables the identification of membrane number and arrangement in multilamellar vesicles, which supports evaluation of drug-loading capacity and encapsulation strategies. Third, in drug delivery studies, the technique facilitates visualization of the spatial localization of drug molecules within liposomes, distinguishing their distribution in aqueous versus lipid phases and elucidating the molecular basis of drug–carrier interactions. Owing to its non-destructive nature and high resolution, Liposome Cryo-EM has emerged as a key analytical tool for quality assessment and process evaluation of liposomal drug formulations.
MtoZ Biolabs provides specialized bioanalytical services encompassing structural characterization, bilayer analysis, particle size determination, and visualization of drug loading within liposomal systems.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
Related Services
How to order?
