Browsing by Author "Monroy, Francisco"
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation.(iScience, 2023) Bouthelier, Antonio; Fernández-Arroyo, Lucía; Mesa-Ciller, Claudia; Cibrian, Danay; Martín-Cófreces, Noa Beatriz; Castillo-González, Raquel; Calero, Macarena; Herráez Aguilar, Diego; Guajardo-Grence, Andrea; Pacheco, Ana María; Marcos-Jiménez, Ana; Quiroga, Borja; Morado, Marta; Monroy, Francisco; Muñoz-Calleja, Cecilia; Sánchez-Madrid, Francisco; Urrutia, Andrés A.; Aragonés, JuliánInhibition of the heterodimeric amino acid carrier SLC7A5/SLC3A2 (LAT1/CD98) has been widely studied in tumor biology but its role in physiological conditions remains largely unknown. Here we show that the SLC7A5/SLC3A2 heterodimer is constitutively present at different stages of erythroid differentiation but absent in mature erythrocytes. Administration of erythropoietin (EPO) further induces SLC7A5/SLC3A2 expression in circulating reticulocytes, as it also occurs in anemic conditions. Although Slc7a5 gene inactivation in the erythrocyte lineage does not compromise the total number of circulating red blood cells (RBCs), their size and hemoglobin content are significantly reduced accompanied by a diminished erythroblast mTORC1 activity. Furthermore circulating Slc7a5-deficient reticulocytes are characterized by lower transferrin receptor (CD71) expression as well as mitochondrial activity, suggesting a premature transition to mature RBCs. These data reveal that SLC7A5/SLC3A2 ensures adequate maturation of reticulocytes as well as the proper size and hemoglobin content of circulating RBCs.Item Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages.(Frontiers in Molecular Biosciences, 2022) Calero, Macarena; Moleiro, Lara H.; Sayd, Aline; Dorca, Yeray; Miquel-Rio, Lluis; Paz, Verónica; Robledo-Montaña, Javier; Enciso, Eduardo; Acción, Fernando; Herráez Aguilar, Diego; Hellweg, Thomas; Sánchez, Luis; Bortolozzi, Analía; Leza, Juan C.; García-Bueno, Borja; Monroy, FranciscoA colloidal synthesis’ proof-of-concept based on the Bligh–Dyer emulsion inversion method was designed for integrating into lipid nanoparticles (LNPs) cell-permeating DNA antisense oligonucleotides (ASOs), also known as GapmeRs (GRs), for mRNA interference. The GR@LNPs were formulated to target brain border-associated macrophages (BAMs) as a central nervous system (CNS) therapy platform for silencing neuroinflammation-related genes. We specifically aim at inhibiting the expression of the gene encoding for lipocalin-type prostaglandin D synthase (L-PGDS), an anti-inflammatory enzyme expressed in BAMs, whose level of expression is altered in neuropsychopathologies such as depression and schizophrenia. The GR@LNPs are expected to demonstrate a bio-orthogonal genetic activity reacting with L-PGDS gene transcripts inside the living system without interfering with other genetic or biochemical circuitries. To facilitate selective BAM phagocytosis and avoid subsidiary absorption by other cells, they were functionalized with a mannosylated lipid as a specific MAN ligand for the mannose receptor presented by the macrophage surface. The GR@LNPs showed a high GR-packing density in a compact multilamellar configuration as structurally characterized by light scattering, zeta potential, and transmission electronic microscopy. As a preliminary biological evaluation of the mannosylated GR@LNP nanovectors into specifically targeted BAMs, we detected in vivo gene interference after brain delivery by intracerebroventricular injection (ICV) in Wistar rats subjected to gene therapy protocol. The results pave the way towards novel gene therapy platforms for advanced treatment of neuroinflammation-related pathologies with ASO@LNP nanovectors.Item Moulding hydrodynamic 2D-crystals upon parametric Faraday waves in shear-functionalized water surfaces.(Nature Communications, 2021) Kharbedia, Mikheil; Caselli, Niccolò; Herráez Aguilar, Diego; López Menéndez, Horacio; Enciso, Eduardo; Santiago, José A.; Monroy, FranciscoFaraday waves, or surface waves oscillating at half of the natural frequency when a liquid is vertically vibrated, are archetypes of ordering transitions on liquid surfaces. Although unbounded Faraday waves patterns sustained upon bulk frictional stresses have been reported in highly viscous fluids, the role of surface rigidity has not been investigated so far. Here, we demonstrate that dynamically frozen Faraday waves—that we call 2D-hydrodynamic crystals—do appear as ordered patterns of nonlinear gravity-capillary modes in water surfaces functionalized with soluble (bio)surfactants endowing in-plane shear stiffness. The phase coherence in conjunction with the increased surface rigidity bears the Faraday waves ordering transition, upon which the hydrodynamic crystals were reversibly molded under parametric control of their degree of order, unit cell size and symmetry. The hydrodynamic crystals here discovered could be exploited in touchless strategies of soft matter and biological scaffolding ameliorated under external control of Faraday waves coherence.Item Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells.(Scientifics Reports, 2020) Herráez Aguilar, Diego; Madrazo, Elena; López Menéndez, Horacio; Ramírez, Manuel; Monroy, Francisco; Redondo Muñoz, JavierThe nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis. By using multiple particle tracking (MPT) technique on chromatin granules, we designed a SURF (Speeded Up Robust Features)-based algorithm to study the mechanical properties of isolated nuclei and in living cells. We have determined the apparent shear stiffness, viscosity and optical density of the nucleus, and how the chromatin structure influences on these biophysical values. Moreover, we used our MPT-SURF analysis to study the apparent mechanical properties of isolated nuclei from patients of acute lymphoblastic leukemia. We found that leukemia cells exhibited mechanical differences compared to normal lymphocytes. Interestingly, isolated nuclei from high-risk leukemia cells showed increased viscosity than their counterparts from normal lymphocytes, whilst nuclei from relapsed-patient's cells presented higher density than those from normal lymphocytes or standard- and high-risk leukemia cells. Taken together, here we presented how MPT-SURF analysis of nuclear chromatin granules defines nuclear mechanical phenotypic features, which might be clinically relevant.