Browsing by Author "Carvalho, Filomena A., 1976-"
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- Studying single-molecule protein interactions and its biological and biomedical applications by AFM-based force spectroscopyPublication . Carvalho, Filomena A., 1976-; Santos, Nuno C., 1972-The use of the knowledge and technology generated by nanomedicine research is slowly gaining its way into the clinical areas. Nanomedicine can be defined as the application of nanotechnologies in medicine, to monitor, diagnose and cure diseases, by using molecular knowledge of the human organism to maintain and improve human health at the molecular scale. In this thesis, we proposed to use force spectroscopy based on atomic force microscopy, a nanotechnology approach, to understand the single-molecule mechanisms involved in two different biomedical relevant systems: (i) Fibrinogen interaction with human blood cell membranes (erythrocytes and platelets) receptors. Increased plasma fibrinogen levels are associated with increased erythrocyte aggregation in cardiovascular diseases. With our results, we identified a specific binding between fibrinogen and an erythrocyte integrin receptor with a β3 or β3-like subunit. This interaction decreases significantly upon erythrocyte aging. We presume that young erythrocytes are the main contributors to the cardiovascular diseases associated with increased fibrinogen content in blood. (ii) Dengue virus (DENV) capsid (C) protein interaction with lipid droplets or lipoproteins. Lipid droplets (LDs) and/or lipoproteins may play an important role on Dengue virus pathogenesis. Our results could explain the key processes occurring in vivo on the Dengue virus replication. We found that DENV C N-terminal region is crucial for the interaction with LDs and very low density lipoproteins (VLDL), requiring the presence of potassium and intrinsic protein(s). Also, pep14-23, a peptide based on the DENV C N-terminal conserved region, inhibits the DENV C-LDs interaction. These findings may be important for the development of C protein-targeted treatments for DENV infections. The main findings described on both of these studies contribute to the establishment of atomic force microscopy as a biomedical tool used to improve knowledge on the molecular mechanisms associated with the development of diseases and their effective treatment.