Biophysics of ophthalmic medications during spaceflight: Principles of ocular fluid dynamics and pharmacokinetics in microgravity.

As spaceflight becomes increasingly accessible and expansive to humanity, it is becoming ever more essential to consider the treatment of various eye diseases in these challenging environments. This paper delves into the increasing fascination with interplanetary travel and its implications for health management in varying environments. It specifically discusses the pharmacological management of ocular diseases, focusing on two key delivery methods: topical eye drops and intravitreal injections. The paper explores how microgravity impacts the administration of these treatments, a vital aspect in understanding drug delivery in space. An extensive analysis is presented on the pharmacokinetics of eye medications, examining the interaction between pharmaceuticals and ocular tissues in zero gravity. The goal of the paper is to bridge the understanding of fluid dynamics, microgravity and the human physiological systems to pave the way for innovative solutions faced by individuals in microgravity.

Squishy to crusty: Biophysics reveal the molecular details of FUS droplet maturation.

In a recent issue of Nature Chemical Biology, Emmanouilidis et al. (2024) investigate the maturation of biomolecular condensates of FUS1-267 and probe the molecular details of droplet aging. They observe that the liquid-to-solid transition of the droplet is mediated at the surface by FUS1-267 molecules that have adopted ß-strand conformations.

APACE: AlphaFold2 and advanced computing as a service for accelerated discovery in biophysics.

The prediction of protein 3D structure from amino acid sequence is a computational grand challenge in biophysics and plays a key role in robust protein structure prediction algorithms, from drug discovery to genome interpretation. The advent of AI models, such as AlphaFold, is revolutionizing applications that depend on robust protein structure prediction algorithms. To maximize the impact, and ease the usability, of these AI tools we introduce APACE, AlphaFold2 and advanced computing as a service, a computational framework that effectively handles this AI model and its TB-size database to conduct accelerated protein structure prediction analyses in modern supercomputing environments. We deployed APACE in the Delta and Polaris supercomputers and quantified its performance for accurate protein structure predictions using four exemplar proteins: 6AWO, 6OAN, 7MEZ, and 6D6U. Using up to 300 ensembles, distributed across 200 NVIDIA A100 GPUs, we found that APACE is up to two orders of magnitude faster than off-the-self AlphaFold2 implementations, reducing time-to-solution from weeks to minutes. This computational approach may be readily linked with robotics laboratories to automate and accelerate scientific discovery.

Computational tools for cellular scale biophysics.

Mathematical models are indispensable for disentangling the interactions through which biological components work together to generate the forces and flows that position, mix, and distribute proteins, nutrients, and organelles within the cell. To illuminate the ever more specific questions studied at the edge of biological inquiry, such models inevitably become more complex. Solving, simulating, and learning from these more realistic models requires the development of new analytic techniques, numerical methods, and scalable software. In this review, we discuss some recent developments in tools for understanding how large numbers of cytoskeletal filaments, driven by molecular motors and interacting with the cytoplasm and other structures in their environment, generate fluid flows, instabilities, and material deformations which help drive crucial cellular processes.

Biophysics-inspired spike rate adaptation for computationally efficient phenomenological nerve modeling.

This study introduces and evaluates the PHAST+ model, part of a computational framework designed to simulate the behavior of auditory nerve fibers in response to the electrical stimulation from a cochlear implant. PHAST+ incorporates a highly efficient method for calculating accommodation and adaptation, making it particularly suited for simulations over extended stimulus durations. The proposed method uses a leaky integrator inspired by classic biophysical nerve models. Through evaluation against single-fiber animal data, our findings demonstrate the model's effectiveness across various stimuli, including short pulse trains with variable amplitudes and rates. Notably, the PHAST+ model performs better than its predecessor, PHAST (a phenomenological model by van Gendt et al.), particularly in simulations of prolonged neural responses. While PHAST+ is optimized primarily on spike rate decay, it shows good behavior on several other neural measures, such as vector strength and degree of adaptation. The future implications of this research are promising. PHAST+ drastically reduces the computational burden to allow the real-time simulation of neural behavior over extended periods, opening the door to future simulations of psychophysical experiments and multi-electrode stimuli for evaluating novel speech-coding strategies for cochlear implants.

Single molecule imaging unveils cellular architecture, dynamics and mechanobiology.

The biomechanical regulation of the cytoskeleton and cell adhesions underlies various essential cellular functions. Studying them requires visualizing their nanostructure and molecular dynamics with evermore precise spatio-temporal resolution. In this review we will focus on the recent advances in single molecule fluorescence imaging techniques and discuss how they improve our understanding of mechanically sensitive cellular structures such as adhesions and the cytoskeleton. We will also discuss future directions for research, emphasizing on the 3D nature of cellular structures and tissues, their mechanical regulation at the molecule level, as well as how super-resolution microscopy will enhance our knowledge on protein structure and conformational changes in the cellular context.

Mechanobiology: Shaping the future of cellular form and function.

Mechanobiology-the field studying how cells produce, sense, and respond to mechanical forces-is pivotal in the analysis of how cells and tissues take shape in development and disease. As we venture into the future of this field, pioneers share their insights, shaping the trajectory of future research and applications.

AAPM Task Group Report 267: A joint AAPM GEC-ESTRO report on biophysical models and tools for the planning and evaluation of brachytherapy.

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments.

Mario Ageno and the status of biophysics.

This essay focuses on Mario Ageno (1915-1992), initially director of the physics laboratory of the Italian National Institute of Health and later professor of biophysics at Sapienza University of Rome. A physicist by training, Ageno became interested in explaining the special characteristics of living organisms origin of life by means of quantum mechanics after reading a book by Schrödinger, who argued that quantum mechanics was consistent with life but that new physical principles must be found. Ageno turned Schrödinger's view into a long-term research project. He aimed to translate Schrödinger's ideas into an experimental programme by building a physical model for at least a very simple living organism. The model should explain the transition from the non-living to the living. His research, however, did not lead to the expected results, and in the 1980s and the 1990s he focused on its epistemological aspect, thinking over the tension between the lawlike structure of physics and the historical nature of biology. His reflections led him to focus on the nature of the theory of evolution and its broader scientific meaning.

Intercomparison of Same-Day Remote Sensing Data for Measuring Winter Cover Crop Biophysical Traits.

Winter cover crops are planted during the fall to reduce nitrogen losses and soil erosion and improve soil health. Accurate estimations of winter cover crop performance and biophysical traits including biomass and fractional vegetative groundcover support accurate assessment of environmental benefits. We examined the comparability of measurements between ground-based and spaceborne sensors as well as between processing levels (e.g., surface vs. top-of-atmosphere reflectance) in estimating cover crop biophysical traits. This research examined the relationships between SPOT 5, Landsat 7, and WorldView-2 same-day paired satellite imagery and handheld multispectral proximal sensors on two days during the 2012-2013 winter cover crop season. We compared two processing levels from three satellites with spatially aggregated proximal data for red and green spectral bands as well as the normalized difference vegetation index (NDVI). We then compared NDVI estimated fractional green cover to in-situ photographs, and we derived cover crop biomass estimates from NDVI using existing calibration equations. We used slope and intercept contrasts to test whether estimates of biomass and fractional green cover differed statistically between sensors and processing levels. Compared to top-of-atmosphere imagery, surface reflectance imagery were more closely correlated with proximal sensors, with intercepts closer to zero, regression slopes nearer to the 1:1 line, and less variance between measured values. Additionally, surface reflectance NDVI derived from satellites showed strong agreement with passive handheld multispectral proximal sensor-sensor estimated fractional green cover and biomass (adj. R2 = 0.96 and 0.95; RMSE = 4.76% and 259 kg ha-1, respectively). Although active handheld multispectral proximal sensor-sensor derived fractional green cover and biomass estimates showed high accuracies (R2 = 0.96 and 0.96, respectively), they also demonstrated large intercept offsets (-25.5 and 4.51, respectively). Our results suggest that many passive multispectral remote sensing platforms may be used interchangeably to assess cover crop biophysical traits whereas SPOT 5 required an adjustment in NDVI intercept. Active sensors may require separate calibrations or intercept correction prior to combination with passive sensor data. Although surface reflectance products were highly correlated with proximal sensors, the standardized cloud mask failed to completely capture cloud shadows in Landsat 7, which dampened the signal of NIR and red bands in shadowed pixels.

State-of-the-Art Molecular Biophysics in Russia.

Thirty years ago, scientists' attention was focused on studying individual molecules, as well as their structure and function [...].

The Best Material from the VII Congress of Russian Biophysicists.

The purpose of this Special Issue is to demonstrate the current state of research in the field of biophysics in the Russian Federation [...].

Biomolecular Condensates Decipher Molecular Codes of Cell Fate: From Biophysical Fundamentals to Therapeutic Practices.

Cell fate is precisely modulated by complex but well-tuned molecular signaling networks, whose spatial and temporal dysregulation commonly leads to hazardous diseases. Biomolecular condensates (BCs), as a newly emerging type of biophysical assemblies, decipher the molecular codes bridging molecular behaviors, signaling axes, and clinical prognosis. Particularly, physical traits of BCs play an important role; however, a panoramic view from this perspective toward clinical practices remains lacking. In this review, we describe the most typical five physical traits of BCs, and comprehensively summarize their roles in molecular signaling axes and corresponding major determinants. Moreover, establishing the recent observed contribution of condensate physics on clinical therapeutics, we illustrate next-generation medical strategies by targeting condensate physics. Finally, the challenges and opportunities for future medical development along with the rapid scientific and technological advances are highlighted.

Impact of Hydrodynamic Interactions on the Kinetic Pathway of Protein Folding.

Protein folding is a fundamental process critical to cellular function and human health, but it remains a grand challenge in biophysics. Hydrodynamic interaction (HI) plays a vital role in the self-organization of soft and biological materials, yet its role in protein folding is not fully understood despite folding occurring in a fluid environment. Here, we use the fluid particle dynamics method to investigate many-body hydrodynamic couplings between amino acid residues and fluid motion in the folding kinetics of a coarse-grained four-α-helices bundle protein. Our results reveal that HI helps select fast folding pathways to the native state without being kinetically trapped, significantly speeding up the folding kinetics compared to its absence. First, the directional flow along the protein backbone expedites protein collapse. Then, the incompressibility-induced squeezing flow effects retard the accumulation of non-native hydrophobic contacts, thus preventing the protein from being trapped in local energy minima during the conformational search of the native structure. We also find that the significance of HI in folding kinetics depends on temperature, with a pronounced effect under biologically relevant conditions. Our findings suggest that HI, particularly the short-range squeezing effect, may be crucial in avoiding protein misfolding.

Editor Profile: Andrey Abramov.

In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Professor Andrey Abramov is a cell biologist and biophysicist at University College London's Queen Square Institute of Neurology. He has served as an Editorial Board Member of The FEBS Journal since 2015.

Lipid Membrane Topographies Are Regulators for the Spatial Distribution of Liquid Protein Condensates.

Liquid protein condensates play important roles in orchestrating subcellular organization and as biochemical reaction hubs. Recent studies have linked lipid membranes to proteins capable of forming liquid condensates, and shown that biophysical parameters, like protein enrichment and restricted diffusion at membranes, regulate condensate formation and size. However, the impact of membrane topography on liquid condensates remains poorly understood. Here, we devised a cell-free system to reconstitute liquid condensates on lipid membranes with microstructured topographies and demonstrated that lipid membrane topography is a significant biophysical regulator. Using membrane surfaces designed with microwells, we observed ordered condensate patterns. Furthermore, we demonstrate that membrane topographies influence the shape of liquid condensates. Finally, we show that capillary forces, mediated by membrane topographies, lead to the directed fusion of liquid condensates. Our results demonstrate that membrane topography is a potent biophysical regulator for the localization and shape of mesoscale liquid protein condensates.

Remembering Jan Amesz (1934-2001): a great gentleman, a major discoverer, and an internationally renowned biophysicist of both oxygenic and anoxygenic photosynthesisa.

We present here the research contributions of Jan Amesz (1934-2001) on deciphering the details of the early physico-chemical steps in oxygenic photosynthesis in plants, algae and cyanobacteria, as well as in anoxygenic photosynthesis in purple, green, and heliobacteria. His research included light absorption and the mechanism of excitation energy transfer, primary photochemistry, and electron transfer steps until the reduction of pyridine nucleotides. Among his many discoveries, we emphasize his 1961 proof, with L. N. M. Duysens, of the "series scheme" of oxygenic photosynthesis, through antagonistic effects of Light I and II on the redox state of cytochrome f. Further, we highlight the following research on oxygenic photosynthesis: the experimental direct proof that plastoquinone and plastocyanin function at their respective places in the Z-scheme. In addition, Amesz's major contributions were in unraveling the mechanism of excitation energy transfer and electron transport steps in anoxygenic photosynthetic bacteria (purple, green and heliobacteria). Before we present his research, focusing on his key discoveries, we provide a glimpse of his personal life. We end this Tribute with reminiscences from three of his former doctoral students (Sigi Neerken; Hjalmar Pernentier, and Frank Kleinherenbrink) and from several scientists (Suleyman Allakhverdiev; Robert Blankenship; Richard Cogdell) including two of the authors (G. Garab and A. Stirbet) of this Tribute.