@article {137340, title = {The ubiquitous nanocluster: A molecular scale organizing principle that governs cellular information flow.}, journal = {Curr Opin Cell Biol}, volume = {86}, year = {2024}, month = {2023 Dec 05}, pages = {102285}, abstract = {

The language of biology at the scale of the cell is constituted of alphabets represented by biomolecules. These are stitched together in a variety of ways to create meaning. We argue that the phrases of this language are nanoscale molecular assemblies or nano-hubs for the purpose of information flow. At the cell surface information is sensed and processed via membrane receptors, often configured as multimers. These nano-assemblies serve as receiver nano-hubs, which are flexibly configured with additional nano-hubs that we term modifiers and transducers. This framework serves to process information that is transmitted for execution inside the cell. Here, we explore some examples about how nano-hubs are built and how they may contribute to cellular information flow.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2023.102285}, author = {Garcia-Parajo, Maria F and Mayor, Satyajit} } @article {126672, title = {Broadband Plasmonic Nanoantennas for Multi-Color Nanoscale Dynamics in Living Cells.}, journal = {Small}, year = {2023}, month = {2023 Mar 31}, pages = {e2207977}, abstract = {

Recently, the implementation of plasmonic nanoantennas has opened new possibilities to investigate the nanoscale dynamics of individual biomolecules in living cells. However, studies so far have been restricted to single molecular species as the narrow wavelength resonance of gold-based nanostructures precludes the simultaneous interrogation of different fluorescently labeled molecules. Here, broadband aluminum-based nanoantennas carved at the apex of near-field probes are exploited to resolve nanoscale-dynamic molecular interactions on living cell membranes. Through multicolor excitation, the authors simultaneously recorded fluorescence fluctuations of dual-color labeled transmembrane receptors known to form nanoclusters. Fluorescence cross-correlation studies revealed transient interactions between individual receptors in regions of ≈60\ nm. Moreover, the high signal-to-background ratio provided by the antenna illumination allowed the authors to directly detect fluorescent bursts arising from the passage of individual receptors underneath the antenna. Remarkably, by reducing the illumination volume below the characteristic receptor nanocluster sizes, the molecular diffusion within nanoclusters is resolved and distinguished from nanocluster diffusion. Spatiotemporal characterization of transient interactions between molecules is crucial to understand how they communicate with each other to regulate cell function. This work demonstrates the potential of broadband photonic antennas to study multi-molecular events and interactions in living cell membranes with unprecedented spatiotemporal resolution.

}, issn = {1613-6829}, doi = {10.1002/smll.202207977}, author = {Sanz-Paz, Maria and van Zanten, Thomas S and Manzo, Carlo and Mivelle, Mathieu and Garcia-Parajo, Maria F} } @article {66088, title = {Dynamic actin-mediated nano-scale clustering of CD44 regulates its meso-scale organization at the plasma membrane.}, journal = {Mol Biol Cell}, volume = {31}, year = {2020}, month = {03/2020}, pages = {561-579}, abstract = {

Transmembrane adhesion receptors at the cell surface, such as CD44, are often equipped with modules to interact with the extracellular-matrix(ECM) and the intra-cellular cytoskeletal machinery. CD44 has been recently shown to compartmentalize the membrane into domains by acting as membrane pickets, facilitating the function of signaling receptors. While spatial organization and diffusion studies of membrane proteins are usually conducted separately, here we combine observations of organization and diffusion by using high spatio-temporal resolution imaging on living cells to reveal a hierarchical organization of CD44. CD44 is present in a meso-scale meshwork pattern where it exhibits enhanced confinement and is enriched in nano-clusters of CD44 along its boundaries. This nanoclustering is orchestrated by the underlying cortical actin dynamics. Interaction with actin is mediated by specific segments of the intracellular-domain(ICD). This influences the organization of the protein at the nano-scale, generating a selective requirement for formin over Arp2/3-based actin-nucleation machinery. The extracellular-domain(ECD) and its interaction with elements of ECM do not influence the meso-scale organization, but may serve to reposition the meshwork with respect to the ECM. Taken together, our results capture the hierarchical nature of CD44 organization at the cell surface, with active cytoskeleton-templated nano-clusters localized to a meso-scale meshwork pattern. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

}, issn = {1939-4586}, doi = {10.1091/mbc.E18-11-0715}, author = {Sil, Parijat and Mateos, Nicolas and Nath, Sangeeta and Buschow, Sonja and Manzo, Carlo and Suzuki, Kenichi G N and Fujiwara, Takahiro and Kusumi, Akihiro and Garcia-Parajo, Maria F and Mayor, Satyajit} }