Serialized on-grid lift-in sectioning for tomography (SOLIST) enables a biopsy at the nanoscale.
Nat Methods
; 21(9): 1693-1701, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39271806
ABSTRACT
Cryo-focused ion beam milling has substantially advanced our understanding of molecular processes by opening windows into cells. However, applying this technique to complex samples, such as tissues, has presented considerable technical challenges. Here we introduce an innovative adaptation of the cryo-lift-out technique, serialized on-grid lift-in sectioning for tomography (SOLIST), addressing these limitations. SOLIST enhances throughput, minimizes ice contamination and improves sample stability for cryo-electron tomography. It thereby facilitates the high-resolution imaging of a wide range of specimens. We illustrate these advantages on reconstituted liquid-liquid phase-separated droplets, brain organoids and native tissues from the mouse brain, liver and heart. With SOLIST, cellular processes can now be investigated at molecular resolution directly in native tissue. Furthermore, our method has a throughput high enough to render cryo-lift-out a competitive tool for structural biology. This opens new avenues for unprecedented insights into cellular function and structure in health and disease, a 'biopsy at the nanoscale'.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microscopía por Crioelectrón
/
Tomografía con Microscopio Electrónico
Límite:
Animals
Idioma:
En
Revista:
Nat Methods
Asunto de la revista:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos