Super-resolution modularity analysis shows that polyhedral caveolin-1 oligomers combine to form scaffolds and caveolae

Network analysis of single molecule super resolution data of caveolin-1 (Cav1) identifies caveolae and 3 distinct non-caveolar Cav1 scaffolds. Here, modularity analysis of endogenous caveolae and scaffolds in HeLa cells shows that small scaffolds combine to form larger scaffolds and caveolae. We leveraged a spectral decomposition algorithm to divide the blob network, based on the eigenvector representation of its adjacency matrix, into modules or communities. The optimization problem of finding modules of a blob involves maximizing intra-connectivity between Cav1 molecules within a module and minimizing inter-connectivity between Cav1 molecules between modules. Features of modules are then matched with intact blobs by finding the similarity between the module-blob pairs of group centers. Our results show that smaller S1A and S1B scaffolds are made up of small polygons, that S1B scaffolds correspond to S1A scaffold dimers and that caveolae and hemi-spherical S2 scaffolds are complex, modular structures formed from S1B and S1A scaffolds, respectively. Polyhedral interactions of Cav1 oligomers therefore leads progressively to the formation of larger and more complex scaffold domains and the biogenesis of caveolae.