Titin – the Spiderweb of the Heart & the Mysterious Protein Novex-3

The story

My research focuses on the giant sarcomeric protein Titin, crucial for heart elasticity. While its striated structure is well-known, imaging heart cells revealed its striking clarity. Our current study examines a smaller Titin isoform, Novex-3, which is upregulated in heart failure tissue compared to donor hearts. Novex-3’s location and function in heart cells remain unclear. 

In this fluorescence micrograph, we imaged Novex-3 alongside Obscurin, revealing Novex-3’s integration into sarcomeres with a distinct pattern. Interestingly, the staining resembles a spiderweb, symbolizing Titin as the heart’s own elastic spiderweb.

Research area

Pathophysiology of heart disease, epigenetics.

Impact

Unraveling the mechanisms of Titin and the role of its various isoforms in heart failure will expand our knowledge of heart failure pathobiology and may reveal novel therapeutical targets for heart failure. Investigating the short Titin isoform Novex-3 represents the first step of this scientific journey.

Image description

The image is protraying nucleic and sarcomeric staining of iPS-derived cardiomyocytes. Nuclei are stained with hoechst (orange). Novex-3 has clear sarcomeric expression (cyan). Obscurin is a protein that is expressed in the sarcomeres (magenta). This image was taken with the Operetta microscope at MultiPark and was subsequently edited in ImarisViewer.

Credits

Julia Martinez, Assistance with image acquisition by Anna Hammarberg, mentoring by Olof Gidlöf and J. Gustav Smith.