Intercellular interactions between cardiomyocytes (CMs) and cardiofibroblasts (FBs) are important in the physiological and pathophysiological heart. Understanding such interactions is important for developing effective heart disease therapies. However, until recently, little has been known about these interactions. We aimed to investigate structural and functional connections between CMs and FBs that are distinct from gap junctions. By membrane dye staining, we observed long, thin membrane nanotubular structures containing actin and microtubules that connected neonatal rat ventricular CMs and FBs. By single-particle tracking, we observed vehicles moving between CMs and FBs within the membrane nanotubes. By dual colour staining, confocal imaging and flow cytometry, we observed mitochondria exchange between CMs and FBs in a coculture system. By combined atomic force microscopy (AFM) and confocal microscopy, we observed calcium signal propagation from AFM-stimulated CM (or FB) to unstimulated FB (or CM) via membrane nanotubes. By membrane and cytoskeleton staining, we observed similar nanotubular structures in adult mouse heart tissue, which suggests their physiological relevance. As a novel type of CM to FB communication, membrane nanotubes observed in vitro and in vivo provide structural and functional connectivity between CMs and FBs over long distances.

In this work, we have developed new aptamer probes for non-small cell lung cancer (NSCLC) by directing the aptamer selection process against the living cells of adenocarcinoma, the most common subtype of NSCLC. A panel of single-stranded DNA (ssDNA) aptamers were generated and evaluated for adenocarcinoma cell recognition. The aptamers bound to the adenocarcinoma cells with dissociation constants in the nanomolar range and the binding of the selected aptamers to the adenocarcinoma cells were significantly stronger than the other cancerous lung cells as well as other types of cancer cells. Moreover, the application of the aptamers to the clinical tissue section samples showed the differentiation of adenocarcinoma from normal lung tissue and other subtypes of lung cancer. The aptamers are expected to be new molecular probes for the investigation of the molecular bases of different NSCLC subtypes and their biological heterogeneity, which is valuable for advancing NSCLC diagnosis and treatment.

Transforming growth factor-β (TGF-β) elicits its signals through two transmembrane serine/threonine kinase receptors, type II (TβRII) and type I receptors. It is generally believed that the initial receptor dimerization is an essential event for receptor activation. However, previous studies suggested that TGF-β signals by binding to the preexisting TβRII homodimer. Here, using single molecule microscopy to image green fluorescent protein (GFP)-labeled TβRII on the living cell surface, we demonstrated that the receptor could exist as monomers at the low expression level in resting cells and dimerize upon TGF-β stimulation. This work reveals a model in which the activation of serine-threonine kinase receptors is also accomplished via dimerization of monomers, suggesting that receptor dimerization is a general mechanism for ligand-induced receptor activation.