A5052577293- Immunotherapy and Immune Responses
- Lipid Membrane Structure and Behavior
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- T-cell and B-cell Immunology
- Probabilistic and Robust Engineering Design
- Cellular transport and secretion
- Spectroscopy and Quantum Chemical Studies
- Genomics and Chromatin Dynamics
- Advanced Fluorescence Microscopy Techniques
- RNA Research and Splicing
- Advanced Biosensing Techniques and Applications
- Immune Cell Function and Interaction
- Estrogen and related hormone effects
- Force Microscopy Techniques and Applications
- Fractional Differential Equations Solutions
- Diffusion and Search Dynamics
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- RNA Interference and Gene Delivery
- Protein Kinase Regulation and GTPase Signaling
- Cell Image Analysis Techniques
- Gene Regulatory Network Analysis
- Virus-based gene therapy research
- Reproductive tract infections research
Institute of Photonic Sciences
2013-2024
Barcelona Institute for Science and Technology
2020-2024
Centre for Genomic Regulation
2020-2022
Harvard University Press
2022
Ragon Institute of MGH, MIT and Harvard
2017
Nonergodicity observed in single-particle tracking experiments is usually modeled by transient trapping rather than spatial disorder. We introduce models of a particle diffusing medium consisting regions with random sizes and diffusivities. The never trapped, but performs continuous Brownian motion the local diffusion constant. Under simple assumptions on distribution diffusivities, we find that mean squared displacement displays subdiffusion due to non-ergodicity for both annealed quenched...
Fundamental biological processes, including the capture of pathogens by membrane receptors, are regulated molecular transport. Scientists show that receptor functioning is linked to nonergodic dynamics, which refers difference between properties a particle and an ensemble particles.
Integrins are cell membrane adhesion receptors involved in morphogenesis, immunity, tissue healing, and metastasis. A central, yet unresolved question regarding the function of integrins is how these regulate both their conformation dynamic nanoscale organization on to generate adhesion-competent microclusters upon ligand binding. Here we exploit high spatial (nanometer) accuracy temporal resolution single-dye tracking dissect relationship between conformational state, lateral mobility,...
Glycan-protein interactions are emerging as important modulators of membrane protein organization and dynamics, regulating multiple cellular functions. In particular, it has been postulated that glycan-mediated regulate surface residence time glycoproteins endocytosis. How this precisely occurs is poorly understood. Here we applied single-molecule-based approaches to directly visualize the impact glycan-based on spatiotemporal interaction with clathrin glycosylated pathogen recognition...
The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora different pathogens. Although it is known that organizes in nanoclusters at the surface DCs, molecular mechanisms responsible for this well defined nanopatterning role viral binding remain enigmatic. By combining biochemical advanced biophysical techniques, including optical superresolution single particle tracking, we demonstrate intrinsic nanoclustering strictly depends its...
Liquid–liquid phase separation (LLPS) is emerging as a key physical principle for biological organization inside living cells, forming condensates that play important regulatory roles. Inside nuclei, transcription factor (TF) regulate transcriptional initiation and amplify the output of expressed genes. However, biophysical parameters controlling TF condensation are still poorly understood. Here we applied battery single-molecule imaging, theory, simulations to investigate properties...
Significance Invariant natural killer T (iNKT) cells react against CD1d antigen-presenting (APCs) in the absence of exogenous antigens, a feature defined as autoreactivity. How iNKT cell autoreactivity is fine-tuned to prevent autoimmunity remains enigmatic. Here, we show that activation regulated by lateral nanoscale organization loaded with and endogenous antigens. Using combination advanced biophysical techniques, molecules organize nanoclusters on membrane APCs. We further discover actin...
Abstract In hormone-responsive breast cancer cells, progesterone (P4) has been shown to act via its nuclear receptor (nPR), a ligand-activated transcription factor. A small fraction of is palmitoylated and anchored the cell membrane (mbPR) forming complex with estrogen alpha (ERα). Upon hormone exposure, either directly or interaction ERα, mbPR activates SRC/RAS/ERK kinase pathway leading phosphorylation nPR by ERK. Kinase activation essential for P4 gene regulation, as ERK MSK1 kinases are...
The spatial organization of membrane receptors at the nanoscale has major implications in cellular function and signaling. advent super-resolution techniques greatly contributed to our understanding membrane. Yet, despite increased resolution, unbiased quantification highly dense features, such as molecular aggregates, remains challenging. Here we describe an algorithm based on Bayesian inference marker intensity distribution that improves determination positions inside nanometer-scale...
Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells culture. This stimulation induces antigen-specific cell proliferation, differentiation into plasma cells, and robust antibody secretion after a few days We validated this strategy using from healthy donors retrieve antibodies against tetanus toxoid influenza hemagglutinin (HA) H1N1 newly...
Abstract The plasma membrane of eukaryotic cells is responsible for a myriad functions that regulate cell physiology and plays crucial role in multitude processes include adhesion, migration, signaling recognition cell–cell communication. This accomplished by specific interactions between different components such as lipids proteins on the lipid bilayer but also through with underlying cortical actin cytoskeleton intracellular side glycocalyx matrix close proximity to extracellular side....
Viral capture and entry to target cells are the first crucial steps that ultimately lead viral infection. Understanding these events is essential toward design development of suitable antiviral drugs and/or vaccines. involves dynamic interactions virus with specific receptors in plasma membrane cells. In last years, single tracking has emerged as a powerful approach assess real time dynamics processes living their engagement cellular components. However, direct visualization early...
ABSTRACT Phase separation is emerging as key principle in the spatiotemporal organization of living cells. Given its relevance regulation numerous biological functions, including gene transcription and chromatin architecture, modeling biomolecular condensation gaining interest. Yet, most models developed so far rely on specific descriptions and/or experimentally inaccessible properties. Here we propose a theoretical model, where phase explained by means interaction probabilities between...
Single particle tracking experiments have recently uncovered that the motion of cell membrane components can undergo changes diffusivity as a result heterogeneous environment, producing subdiffusion and nonergodic behavior. In this paper, we show an autoregressive fractionally integrated moving average (ARFIMA) with noise given by generalized conditional heteroscedasticity (GARCH) describe inhomogeneous diffusion in membrane, where ARFIMA process models anomalous GARCH explains fluctuating parameter.
Abstract Direct visualization of the early steps multi-receptor viral interactions at singlemolecule level has been largely impeded by technical challenges associated to imaging individual multi-molecular systems relevant spatial (nanometer) and temporal (millisecond) scales. Here, we present a four-color, high-density single-molecule spatiotemporal mapping methodology capture real-time between viruses three different (co-)receptors on membrane living immune cells derived from donors....