Imagining the future of optical microscopy: everything, everywhere, all at once

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Окт. 28, 2023

The optical microscope has revolutionized biology since at least the 17

Язык: Английский

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TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 18, 2023

Abstract TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or competition of shared ligands. Whether directly delivers cell-intrinsic signals remains unclear. Here we show, analysing from matched human tumour peripheral blood samples, that co-expression rare tumour-infiltrating lymphocytes. Using super-resolution microscopy other techniques, demonstrate ligation with CD155 causes to reorganise into dense nanoclusters, which coalesce cell (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion a manner dependent TIGIT’s intracellular ITT-like signalling motif. Thus, provide evidence inhibits lymphocyte activation, acting independently CD226, requiring proximal the TCR. Within subset tumours where TIGIT-expressing do not commonly co-express will likely be dominant mechanism action.

Язык: Английский

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Single-Molecule Displacement Mapping Unveils Sign-Asymmetric Protein Charge Effects on Intraorganellar Diffusion

Nano Letters, Год журнала: 2023, Номер 23(5), С. 1711 - 1716

Опубликована: Фев. 20, 2023

Using single-molecule displacement/diffusivity mapping (SM

Язык: Английский

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Biomimetic Nanomodulators With Synergism of Photothermal Therapy and Vessel Normalization for Boosting Potent Anticancer Immunity

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

Abstract Combination therapy using photothermal (PTT) and immunotherapy is one of the most promising approaches for eliciting host immune responses to ablate tumors. However, its therapeutic efficacy limited due inefficient cell infiltration cellular responses. In this study, a biomimetic immunostimulatory nanomodulator, Tm@PDA‐GA (4T1 membrane@polydopamine‐gambogic acid), with homologous targeting developed. The 4T1 membrane (Tm) coating reduced immunogenicity facilitated uptake by tumor cells. Polydopamine (PDA) as drug carrier can induce PTT under near‐infrared ray (NIR) irradiation immunogenic death (ICD) activate dendritic cells (DCs). Moreover, on‐demand released gambogic acid (GA) in an acidic microenvironment, inhibiting expression heat shock proteins (HSPs) synergetic chemo‐photothermal anti‐tumor activity increasing ICD More importantly, GA normalize vessels via HIF‐1α VEGF inhibition enhance alleviate hypoxia stress. Thus, induced ICD, activated DCs, stimulated cytotoxic T cells, suppressed Tregs. combined anti‐PD‐L1 further augment response effectively suppress growth lung metastasis. conclusion, biomaterial‐mediated vessel normalization strategy effective triple‐negative breast cancer (TNBC).

Язык: Английский

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Single-Molecule Spectroscopy and Super-Resolution Mapping of Physicochemical Parameters in Living Cells

Annual Review of Physical Chemistry, Год журнала: 2024, Номер 75(1), С. 163 - 183

Опубликована: Фев. 16, 2024

By superlocalizing the positions of millions single molecules over many camera frames, a class super-resolution fluorescence microscopy methods known as single-molecule localization (SMLM) has revolutionized how we understand subcellular structures past decade. In this review, highlight emerging studies that transcend outstanding structural (shape) information offered by SMLM to extract and map physicochemical parameters in living mammalian cells at levels. encoding/decoding high-dimensional information-such emission excitation spectra, motion, polarization, lifetime, beyond-for every molecule, mass accumulating these measurements for molecules, such multidimensional multifunctional approaches open new windows into intracellular architectures dynamics, well their underlying biophysical rules, far beyond diffraction limit.

Язык: Английский

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Single-Molecule Displacement Mapping Indicates Unhindered Intracellular Diffusion of Small (≲1 kDa) Solutes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(15), С. 8510 - 8516

Опубликована: Апрель 7, 2023

While fundamentally important, the intracellular diffusion of small (≲1 kDa) solutes has been difficult to elucidate due challenges in both labeling and measurement. Here we quantify spatially map translational patterns mammalian cells by integrating several recent advances. In particular, executing tandem stroboscopic illumination pulses down 400 μs separation, extend single-molecule displacement/diffusivity mapping (SMdM), a super-resolution quantification tool, with high coefficients

Язык: Английский

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Multidimensional Super-Resolution Microscopy Unveils Nanoscale Surface Aggregates in the Aging of FUS Condensates

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(44), С. 24240 - 24248

Опубликована: Окт. 2, 2023

The intracellular liquid–liquid phase separation (LLPS) of biomolecules gives rise to condensates that act as membrane-less organelles with vital functions. FUS, an RNA-binding protein, natively forms through LLPS and further provides a model system for the often disease-linked liquid-to-solid transition biomolecular during aging. However, mechanism such maturation processes, well structural physical properties system, remains unclear, partly attributable difficulties in resolving internal structures micrometer-sized diffraction-limited optical microscopy. Harnessing set multidimensional super-resolution microscopy tools uniquely map out local physicochemical parameters single-molecule spectroscopy, here, we uncover nanoscale heterogeneities FUS elucidate their evolution over Through spectrally resolved localization (SR-SMLM) solvatochromic dye, unveil distinct hydrophobic nanodomains at condensate surface. SMLM fluorogenic amyloid probe, identify these aggregates. displacement/diffusivity mapping (SMdM), show nanoaggregates drastically impede diffusion. Notably, upon aging or mechanical shears, progressively expand on surface, thus leading growing low-diffusivity shell while leaving interior diffusion-permitting. Together, beyond uncovering fascinating arrangements mechanisms single-component condensates, demonstrated synergy approaches this study opens new paths understanding systems nanoscale.

Язык: Английский

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Tetra-color superresolution microscopy based on excitation spectral demixing

Light Science & Applications, Год журнала: 2023, Номер 12(1)

Опубликована: Янв. 2, 2023

Multicolor imaging allows protein colocalizations and organelle interactions to be studied in biological research, which is especially important for single-molecule localization microscopy (SMLM). Here, we propose a multicolor method called excitation-resolved stochastic optical reconstruction (ExR-STORM). The method, based on the excitation spectrum of fluorescent dyes, successfully separated four spectrally very close far-red organic fluorophores utilizing three lasers with cross-talk less than 3%. Dyes that are only 5 nm apart emission were resolved, resulting negligible chromatic aberrations. This was extended three-dimensional (3D) by combining astigmatic providing powerful tool resolving 3D morphologies at nanoscale.

Язык: Английский

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Displacement Statistics of Unhindered Single Molecules Show no Enhanced Diffusion in Enzymatic Reactions

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(11), С. 4839 - 4844

Опубликована: Март 8, 2022

Recent studies have sparked debate over whether catalytic reactions enhance the diffusion coefficients

Язык: Английский

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The power of super-resolution microscopy in modern biomedical science

Advances in Colloid and Interface Science, Год журнала: 2023, Номер 314, С. 102880 - 102880

Опубликована: Март 13, 2023

Язык: Английский

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