Super-resolution microscopy at its sharpest

AdMaPlace March 13, 2025

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First, it is becoming important to explore how such high levels of precision can be reliably translated to biomedical imaging settings while coping with the complexity inherent to the biological world. For this reason, optics-driven advancements in super-resolution microscopy must involve close collaboration with biologists, to understand their needs and what questions need answers. Meaningful development is often initiated, and then driven, by asking the right questions and finding the right problem to solve, aligning efforts with real needs. Collaboration with (bio)chemists is also important to make sure labelling workflows are feasible and reliable.

Second, as spatial resolution approaches the size of fluorophores themselves, we enter what is often referred to as nanoscopy. Although this opens up exciting possibilities for studying proteins and potentially their conformational changes with unprecedented detail, it also comes with challenges. Labelling samples at such an extreme scale is difficult, as existing methods struggle to attach fluorescent tags just a few nanometres apart within cells. We also need to deal with the different photochemistry of two fluorophores spaced by less than 10 nm, as their photo-switching behaviour can be altered, reducing the probability of accurate localization. Importantly, this challenge is shared across multiple techniques, showing the importance of finding solutions.

Finally, the ability to image live cells over long periods of time is highly valued when it comes to studying dynamical processes in real time. However, super-resolution microscopy works best with fixed samples. Live cells are mobile, thus demanding careful optimization of the trade-off between spatial resolution, imaging speed and field of view. Hours-long imaging also raises challenges of phototoxicity and photobleaching, and it highlights the need for new fluorescent probes that are both stable and non-invasive over long periods.

Overall, this Focus issue attempts to capture a selection of recent developments and spark discussions about new opportunities and outstanding challenges to increase our understanding of the biological world. Through synergistic efforts from optics, biology and biochemistry, super-resolution microscopy is poised to keep developing, gain wider adoption and provide solutions to real-world biomedical challenges that can tangibly improve healthcare and clinical outcomes.

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Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects

The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.

AdMaPlace March 9, 2025

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Type 2 immunity in allergic diseases

Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.

AdMaPlace March 9, 2025

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Engineering bone/cartilage organoids: strategy, progress, and application

The concept and development of bone/cartilage organoids are rapidly gaining momentum, providing opportunities for both fundamental and translational research in bone biology. Bone/cartilage organoids, essentially miniature bone/cartilage tissues grown in vitro, enable the study of complex cellular interactions, biological processes, and disease pathology in a representative and controlled environment. This review provides a comprehensive and up-to-date overview of the field, focusing on the strategies for bone/cartilage organoid construction strategies, progresses in the research, and potential applications. We delve into the significance of selecting appropriate cells, matrix gels, cytokines/inducers, and construction techniques. Moreover, we explore the role of bone/cartilage organoids in advancing our understanding of bone/cartilage reconstruction, disease modeling, drug screening, disease prevention, and treatment strategies. While acknowledging the potential of these organoids, we discuss the inherent challenges and limitations in the field and propose potential solutions, including the use of bioprinting for organoid induction, AI for improved screening processes, and the exploration of assembloids for more complex, multicellular bone/cartilage organoids models. We believe that with continuous refinement and standardization, bone/cartilage organoids can profoundly impact patient-specific therapeutic interventions and lead the way in regenerative medicine.

AdMaPlace March 9, 2025

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$Diffraction minima resolve point scatterers at few hundredths of the wavelength$

Diffraction minima resolve point scatterers at few hundredths of the wavelength

Resolving two or more constantly scattering identical point sources using freely propagating waves is limited by diffraction. Here we show that, by illuminating with a diffraction minimum, a given number of point scatterers can be resolved at distances of small fractions of the wavelength. Specifically, we identify an 8 nm distance, which corresponds to 1/80 of the employed 640 nm wavelength, between two constantly emitting fluorescent molecules in the focal plane of an optical microscope. We also measure 22 nm side length for a quadratic array of four molecules. Moreover, we show that the measurement precision improves with decreasing distance and with increased scatterer density. This work opens up the prospect of resolving individual scatterers in clusters that are far smaller than the wavelength.

AdMaPlace March 13, 2025

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Optical sorting: past, present and future

Optical sorting combines optical tweezers with diverse techniques, including optical spectrum, artificial intelligence (AI) and immunoassay, to endow unprecedented capabilities in particle sorting. In comparison to other methods such as microfluidics, acoustics and electrophoresis, optical sorting offers appreciable advantages in nanoscale precision, high resolution, non-invasiveness, and is becoming increasingly indispensable in fields of biophysics, chemistry, and materials science. This review aims to offer a comprehensive overview of the history, development, and perspectives of various optical sorting techniques, categorised as passive and active sorting methods. To begin, we elucidate the fundamental physics and attributes of both conventional and exotic optical forces. We then explore sorting capabilities of active optical sorting, which fuses optical tweezers with a diversity of techniques, including Raman spectroscopy and machine learning. Afterwards, we reveal the essential roles played by deterministic light fields, configured with lens systems or metasurfaces, in the passive sorting of particles based on their varying sizes and shapes, sorting resolutions and speeds. We conclude with our vision of the most promising and futuristic directions, including AI-facilitated ultrafast and bio-morphology-selective sorting. It can be envisioned that optical sorting will inevitably become a revolutionary tool in scientific research and practical biomedical applications.

AdMaPlace March 11, 2025

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