Cryo-electron tomography reveals the structural diversity of cardiac proteins in their cellular context.
bioRxiv : the preprint server for biology
Cardiovascular diseases are a leading cause of death worldwide, but our understanding of the underlying mechanisms is limited, in part because of the complexity of the cellular machinery that controls the heart muscle contraction cycle. Cryogenic electron tomography (cryo-ET) provides a way to visualize diverse cellular machinery while preserving contextual information like subcellular localization and transient complex formation, but this approach has not been widely applied to the study of heart muscle cells (cardiomyocytes). Here, we deploy a platform for studying cardiovascular disease by combining cryo-ET with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). After developing a cryo-ET workflow for visualizing macromolecules in hiPSC-CMs, we reconstructed sub-nanometer resolution structures of the human thin filament, a central component of the contractile machinery. We also visualized a previously unobserved organization of a regulatory complex that connects muscle contraction to calcium signaling (the troponin complex), highlighting the value of our approach for interrogating the structures of cardiac proteins in their cellular context.
View details for DOI 10.1101/2023.10.26.564098
View details for PubMedID 37961228
View details for PubMedCentralID PMC10634850
The Z-disc: Mechanosensor at the interface between myosin biomechanics and hypertrophic signaling
CELL PRESS. 2023: 404A
View details for Web of Science ID 000989629702211
- The Z-disc: Mechanosensor at the interface between myosin biomechanics and hypertrophic signaling. Biophysical journal 2023; 122 (3S1): 404a