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- Bernardi, Anna, et al.
(author)
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Multivalent glycoconjugates as anti-pathogenic agents
- 2013
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In: Chemical Society Reviews. - : Royal Society of Chemistry (RSC). - 0306-0012 .- 1460-4744. ; 42:11, s. 4709-4727
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Research review (peer-reviewed)abstract
- Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.
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2. |
- Monzo, Pascale, et al.
(author)
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Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion
- 2021
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In: Developmental Cell. - : Elsevier. - 1534-5807 .- 1878-1551. ; 56:20, s. 2841-2855.e8
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Journal article (peer-reviewed)abstract
- Glioblastoma are heterogeneous tumors composed of highly invasive and highly proliferative clones, Heterogeneity in invasiveness could emerge from discrete biophysical properties linked to specific molecular expression. We identified clones of patient-derived glioma propagating cells that were either highly proliferative or highly invasive and compared their cellular architecture, migratory, and biophysical properties. We discovered that invasiveness was linked to cellular fitness. The most invasive cells were stiffer, developed higher mechanical forces on the substrate, and moved stochastically. The mechano-chemical-induced expression of the formin FMN1 conferred invasive strength that was confirmed in patient samples. Moreover, FMN1 expression was also linked to motility in other cancer and normal cell lines, and its ectopic expression increased fitness parameters. Mechanistically, FMN1 acts from the microtubule lattice and promotes a robust mechanical cohesion, leading to highly invasive motility.
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