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Supramolecular systems generated by peptide-saccharide conjugates to mimic the ...
Costa, Diana Soares da; Brito, Alexandra Manuela Fernandes; Reis, R. L.; Pashkuleva, I.Carbohydrates and proteins are the main constituents of the extracellular matrix (ECM). Their supramolecular hierarchical assembly results in cell- and tissue-specific signatures that are tightly controlled in terms of biomechanical forces and biochemical functions. Over the last decade, supramolecular glycopeptide systems have emerged as synthetic mimics of the ECM. Their main advantage is the simpler structur...
Inhibiting cancer metabolism by aromatic carbohydrate amphiphiles that act as a...
Brito, Alexandra; Pereira, Patrícia M.; Costa, Diana Soares da; Reis, R. L.; Ulijn, Rein V.; Lewis, Rein V.; Pires, R. A.; Pashkuleva, I.We report on aromatic N-glucosides that inhibit selectively the cancer metabolism via two coexistent mechanisms: by initial deprivation of the glucose uptake through competitive binding in the glucose binding pocket of GLUT1 and by formation of a sequestering nanoscale supramolecular network at the cell surface through localized (biocatalytic) self-assembly. We demonstrate that the expression of the cancer asso...
Hyaluronic acid of low molecular weight triggers the invasive “hummingbird” phe...
Amorim, Sara; Costa, Diana Soares da; Pashkuleva, Iva; Reis, Celso A.; Reis, R. L.; Pires, R. A.The overproduction and deposition of hyaluronic acid (HA) of different sizes in the tumor microenvironment is associated with cancer metastasis. Here, the development of layerâ byâ layer (LbL) constructs containing HA of different molecular weights (i.e., 5.6, 618, and 1450Â kDa) that mimic the HAâ rich cancer extracellular matrix is described to study the effect of the HA's size on the behavior of gastric canc...
Extracellular matrix-inspired assembly of glycosaminoglycan-collagen fibers
Carretero, Agatha; Costa, Diana Soares da; Reis, R. L.; Pashkuleva, I.We report on the fabrication of fibers exclusively from extracellular matrix components by interfacial complexation with no use of any crosslinking agent. The obtained fibers may have different biomedical applications as they are flexible, cell adhere to and remodel them. Moreover, their stability and thickness can be finely tuned by the sulfation degree of the used glycosaminoglycans.
Design of protein delivery systems by mimicking extracellular mechanisms for pr...
Silva, C.; Carretero, Agatha; Costa, Diana Soares da; Reis, R. L.; Novoa-Carballal, R.; Pashkuleva, I.Heparin sulfate proteoglycans (HSPGs) are responsible for the storage and stabilization of numerous growth factors in the extracellular matrix. In this complex native environment, the efficient binding of the growth factors is determined by multivalent, specific and reversible electrostatic interactions between the sulfate groups of HSPGs and the positively charged amino acids of the growth factor. Inspired by ...
Sulfation of glycosaminoglycans and its Implications in human health and disorders
Costa, Diana Soares da; Reis, R. L.; Pashkuleva, I.Sulfation is a dynamic and complex posttranslational modification process. It can occur at various positions within the glycosaminoglycan (GAG) backbone and modulates extracellular signals such as cellâ cell and cellâ matrix interactions; different sulfation patterns have been identified for the same organs and cells during their development. Because of their high specificity in relation to function, GAG sulfat...
Fabrication and characterization of Eri silk fibers-based sponges for biomedica...
Silva, Simone Santos; Oliveira, Nuno M.; Oliveira, Mariana Braga; Costa, Diana Soares da; Naskar, Deboki; Mano, J. F.; Kundu, S. C.; Reis, R. L.Cocoon-derived semi-domesticated Eri silk fibers still lack exploitation for tissue engineering applications due to their poor solubility using conventional methods. The present work explores the ability to process cocoon fibers of non-mulberry Eri silk (Samia/Philosamia ricini) into sponges through a green approach using ionic liquid (IL) â 1-buthyl-imidazolium acetate as a solvent. The formation of β-sheet s...
Surfaces mimicking glycosaminoglycans trigger different response of stem cells ...
Araújo, A. R.; Costa, Diana Soares da; Amorim, Sara; Reis, R. L.; Pires, R. A.; Pashkuleva, I.We report on the utility of a platform created by self-assembled monolayers to investigate the influence of the degree of sulfation of glycosaminoglycans (GAGs) on their interactions with fibronectin (Fn) and the impact of these interactions on the adhesion and morphology of human adipose derived stem cells (ASCs). We used the label-free QCM-D, AFM and SPR to follow the changes in the protein adlayer in close p...
Controlling cancer cell fate using localized biocatalytic self-assembly of an a...
Pires, R. A.; Abul-Haija, Yousef M.; Costa, Diana Soares da; Novoa-Carballal, R.; Reis, R. L.; Ulijn, R. V.; Pashkuleva, I.We report on a simple carbohydrate amphiphile able to self-assemble into nanofibers upon enzymatic dephosphorylation. The self-assembly can be triggered by alkaline phosphatase (ALP) in solution or in situ by the ALP produced by osteosarcoma cell line, SaOs2. In the latter case, assembly and localized gelation occurs mainly on the cell surface. The gelation of the pericellular environment induces a reduction of...
Adhesion of adipose-derived mesenchymal stem cells to glycosaminoglycan surface...
Costa, Diana Soares da; Márquez-Posadas, M. C.; Araújo, A. R.; Yang, Y.; Merino, S.; Groth, T.; Reis, R. L.; Pashkuleva, I.Proteins and glycosaminoglycans (GAGs) are main constituents of the extracellular matrix (ECM). They act in synergism and are equally critical for the development, growth, function or survival of an organism. In this work, we developed surfaces that display these two classes of biomacromolecules, namely GAGs and proteins, in spatially controlled fashion. The generated surfaces can be used as a minimalistic but ...