Torsion affects the calculation of DNA twisting number.

The topological properties of DNA have long been a focal point in biophysics. In the 1970s, White proposed that the topology of closed DNA double helix follows White's formula: Lk=Wr+Tw. However, there has been controversy in the calculation of DNA twisting number, partly due to discrepancies in the definition of torsion in differential geometry. In this paper, we delved into a detailed study of torsion, revealing that the calculation of DNA twisting number should use the curve's geodesic torsion. Furthermore, we found that the discrepancy in DNA twisting numbers calculated using different torsion is N. This study elucidated the impact of torsion on the calculation of DNA twisting numbers, aiming to resolve controversies in the calculation of DNA topology and provided accurate computational methods and theoretical foundations for related research.

The Three-Dimensional Reference Interaction Site Model Approach as a Promising Tool for Studying Hydrated Viruses and Their Complexes with Ligands.

Viruses are the most numerous biological form living in any ecosystem. Viral diseases affect not only people but also representatives of fauna and flora. The latest pandemic has shown how important it is for the scientific community to respond quickly to the challenge, including critically assessing the viral threat and developing appropriate measures to counter this threat. Scientists around the world are making enormous efforts to solve these problems. In silico methods, which allow quite rapid obtention of, in many cases, accurate information in this field, are effective tools for the description of various aspects of virus activity, including virus-host cell interactions, and, thus, can provide a molecular insight into the mechanism of virus functioning. The three-dimensional reference interaction site model (3D-RISM) seems to be one of the most effective and inexpensive methods to compute hydrated viruses, since the method allows us to provide efficient calculations of hydrated viruses, remaining all molecular details of the liquid environment and virus structure. The pandemic challenge has resulted in a fast increase in the number of 3D-RISM calculations devoted to hydrated viruses. To provide readers with a summary of this literature, we present a systematic overview of the 3D-RISM calculations, covering the period since 2010. We discuss various biophysical aspects of the 3D-RISM results and demonstrate capabilities, limitations, achievements, and prospects of the method using examples of viruses such as influenza, hepatitis, and SARS-CoV-2 viruses.

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.

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.

The cryo-EM structure of ASK1 reveals an asymmetric architecture allosterically modulated by TRX1.

Apoptosis signal-regulating kinase 1 (ASK1) is a crucial stress sensor, directing cells toward apoptosis, differentiation, and senescence via the p38 and JNK signaling pathways. ASK1 dysregulation has been associated with cancer and inflammatory, cardiovascular, and neurodegenerative diseases, among others. However, our limited knowledge of the underlying structural mechanism of ASK1 regulation hampers our ability to target this member of the MAP3K protein family towards developing therapeutic interventions for these disorders. Nevertheless, as a multidomain Ser/Thr protein kinase, ASK1 is regulated by a complex mechanism involving dimerization and interactions with several other proteins, including thioredoxin 1 (TRX1). Thus, the present study aims at structurally characterizing ASK1 and its complex with TRX1 using several biophysical techniques. As shown by cryo-EM analysis, in a state close to its active form, ASK1 is a compact and asymmetric dimer, which enables extensive interdomain and interchain interactions. These interactions stabilize the active conformation of the ASK1 kinase domain. In turn, TRX1 functions as a negative allosteric effector of ASK1, modifying the structure of the TRX1-binding domain and changing its interaction with the tetratricopeptide repeats domain. Consequently, TRX1 reduces access to the activation segment of the kinase domain. Overall, our findings not only clarify the role of ASK1 dimerization and inter-domain contacts but also provide key mechanistic insights into its regulation, thereby highlighting the potential of ASK1 protein-protein interactions as targets for anti-inflammatory therapy.

Mechanobiology of the nucleus during the G2-M transition.

Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.

Unveiling Mechanobiology: A Compact Device for Uniaxial Mechanical Stimulation on Nanofiber Substrates and Its Impact on Cellular Behavior and Nanoparticle Distribution.

Biotechnology and its allied sectors, such as tissue culture, regenerative medicine, and personalized medicine, primarily rely upon extensive studies on cellular behavior and their molecular pathways for generating essential knowledge and innovative strategies for human survival. Most such studies are performed on flat, adherent, plastic-based surfaces and use nanofiber and hydrogel-like soft matrices from the past few decades. However, such static culture conditions cannot mimic the immediate cellular microenvironment, where they perceive or generate a myriad of different mechanical forces that substantially affect their downstream molecular pathways. Including such mechanical forces, still limited to specialized laboratories, using a few commercially available or noncommercial technologies are gathering increasing attention worldwide. However, large-scale consideration and adaptation by developing nations have yet to be achieved due to the lack of a cost-effective, reliable, and accessible solution. Moreover, investigations on cellular response upon uniaxial mechanical stretch cycles under more in vivo mimetic conditions are yet to be studied comprehensively. In order to tackle these obstacles, we have prepared a compact, 3D-printed device using a microcontroller, batteries, sensors, and a stepper motor assembly that operates wirelessly and provides cyclic mechanical attrition to any thin substrate. We have fabricated water-stable and stretchable nanofiber substrates with different fiber orientations by using the electrospinning technique to investigate the impact of mechanical stretch cycles on the morphology and orientation of C2C12 myoblast-like cells. Additionally, we have examined the uptake and distribution properties of BSA-epirubicin nanoparticles within cells under mechanical stimulation, which could act as fluorescently active drug-delivery agents for future therapeutic applications. Consequently, our research offers a comprehensive analysis of cellular behavior when cells are subjected to uniaxial stretching on various nanofiber mat architectures. Furthermore, we present a cost-effective alternative solution that addresses the long-standing requirement for a compact, user-friendly, and tunable device, enabling more insightful outcomes in mechanobiology.

Optimal control of ribosome population for gene expression under periodic nutrient intake.

Translation of proteins is a fundamental part of gene expression that is mediated by ribosomes. As ribosomes significantly contribute to both cellular mass and energy consumption, achieving efficient management of the ribosome population is also crucial to metabolism and growth. Inspired by biological evidence for nutrient-dependent mechanisms that control both ribosome-active degradation and genesis, we introduce a dynamical model of protein production, that includes the dynamics of resources and control over the ribosome population. Under the hypothesis that active degradation and biogenesis are optimal for maximizing and maintaining protein production, we aim to qualitatively reproduce empirical observations of the ribosome population dynamics. Upon formulating the associated optimization problem, we first analytically study the stability and global behaviour of solutions under constant resource input, and characterize the extent of oscillations and convergence rate to a global equilibrium. We further use these results to simplify and solve the problem under a quasi-static approximation. Using biophysical parameter values, we find that optimal control solutions lead to both control mechanisms and the ribosome population switching between periods of feeding and fasting, suggesting that the intense regulation of ribosome population observed in experiments allows to maximize and maintain protein production. Finally, we find some range for the control values over which such a regime can be observed, depending on the intensity of fasting.

Tau Oligomers as Pathogenic Seeds: Preparation, Characterization, and Propagation In Vitro and In Vivo.

Tau oligomers have been shown to be the main toxic tau species in several neurodegenerative disorders. To study tau oligomers, we have developed reagents and established methods for the reliable preparation, isolation, and detection of tau oligomers as well as their seeding and propagation both in vitro and in vivo. Detailed below are methods for isolation of tau oligomers from brain tissues and detection of tau oligomers using tau oligomer-specific antibodies by biochemical, immunohistochemical, and biophysical methods. Further, methods for evaluating the biological activity of the tau oligomers including their effects on synaptic function, seeding, and propagation in cell models and in vivo are also described.

How neuronal morphology impacts the synchronisation state of neuronal networks.

The biophysical properties of neurons not only affect how information is processed within cells, they can also impact the dynamical states of the network. Specifically, the cellular dynamics of action-potential generation have shown relevance for setting the (de)synchronisation state of the network. The dynamics of tonically spiking neurons typically fall into one of three qualitatively distinct types that arise from distinct mathematical bifurcations of voltage dynamics at the onset of spiking. Accordingly, changes in ion channel composition or even external factors, like temperature, have been demonstrated to switch network behaviour via changes in the spike onset bifurcation and hence its associated dynamical type. A thus far less addressed modulator of neuronal dynamics is cellular morphology. Based on simplified and anatomically realistic mathematical neuron models, we show here that the extent of dendritic arborisation has an influence on the neuronal dynamical spiking type and therefore on the (de)synchronisation state of the network. Specifically, larger dendritic trees prime neuronal dynamics for in-phase-synchronised or splayed-out activity in weakly coupled networks, in contrast to cells with otherwise identical properties yet smaller dendrites. Our biophysical insights hold for generic multicompartmental classes of spiking neuron models (from ball-and-stick-type to anatomically reconstructed models) and establish a connection between neuronal morphology and the susceptibility of neural tissue to synchronisation in health and disease.

Engines of change: Nonmuscle myosin II in mechanobiology.

The emergence of mechanobiology has unveiled complex mechanisms by which cells adjust intracellular force production to their needs. Most communicable intracellular forces are generated by myosin II, an actin-associated molecular motor that transforms adenosine triphosphate (ATP) hydrolysis into contraction in nonmuscle and muscle cells. Myosin II-dependent force generation is tightly regulated, and deregulation is associated with specific pathologies. Here, we focus on the role of myosin II (nonmuscle myosin II, NMII) in force generation and mechanobiology. We outline the regulation and molecular mechanism of force generation by NMII, focusing on the actual outcome of contraction, that is, force application to trigger mechanosensitive events or the building of dissipative structures. We describe how myosin II-generated forces drive two major types of events: modification of the cellular morphology and/or triggering of genetic programs, which enhance the ability of cells to adapt to, or modify, their microenvironment. Finally, we address whether targeting myosin II to impair or potentiate its activity at the motor level is a viable therapeutic strategy, as illustrated by recent examples aimed at modulating cardiac myosin II function in heart disease.

Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study).

Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD] = 5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate, and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches.

From gene to mechanics: a comprehensive insight into the mechanobiology of LMNA mutations in cardiomyopathy.

Severe cardiac remodeling leading to heart failure in individuals harboring pathogenic LMNA variants, known as cardiolaminopathy, poses a significant clinical challenge. Currently, there is no effective treatment for lamin-related diseases. Exploring the intricate molecular landscape underlying this condition, with a specific focus on abnormal mechanotransduction, will propel our understanding of cardiolaminopathy. The LMNA gene undergoes alternative splicing to create A-type lamins, a part of the intermediate filament protein family. A-type lamins are located underneath the nuclear envelope, and given their direct interaction with chromatin, they serve as mechanosensory of the cell by interacting with the cytoskeleton and safeguarding the transcriptional program of cells. Nucleated cells in the cardiovascular system depend on precise mechanical cues for proper function and adaptation to stress. Mechanosensitive signaling pathways are essential in regulating mechanotransduction. They play a pivotal role in various molecular and cellular processes and commence numerous downstream effects, leading to transcriptional activation of target genes involved in proliferation, migration, and (anti-)apoptosis. Most pathways are known to be regulated by kinases, and this area remains largely understudied in cardiomyopathies.Heart failure is linked to disrupted mechanotransduction, where LMNA mutations affect nuclear integrity, impacting the response to extracellular matrix signals and the environment. The Hippo pathway, anchored by YAP1/WWTR1, emerges as a central player by orchestrating cellular responses to mechanical signals. However, the involvement of Hippo and YAP1/WWTR1 in cardiolaminopathy is unclear and likely mutation- and tissue-specific, warranting further investigation. Here, we highlight the involvement of multiple signaling pathways in mechanotransduction in cardiolaminopathy. We delve into (non-)canonical functions of key signaling components, which may hold critical clues for understanding disease pathogenesis. In summary, we comprehensively examine the mechanobiology of A-type lamins, the role of mechanosensitive signaling pathways, and their intricate interplay in the pathogenesis of cardiolaminopathy. A better understanding of these mechanisms is paramount for developing targeted therapies and interventions for individuals afflicted with this debilitating cardiac condition. Prior studies overlooked accurate gene nomenclature in protein and pathway names. Our review addresses this gap, ensuring precision by aligning names with correct gene nomenclature.

Mutations in the A-type lamin gene (LMNA) can cause a laminopathy. A specific manifestation of this disease leads to cardiolaminopathy, a serious heart condition. The lamin network, located at the inner nuclear membrane, is a central player in transforming forces within cells. As cells move and function, they rely on the ability to sense and respond to these forces, a process named mechanosensing and -response. This review provides an overview of the key molecular pathways involved in the development of heart failure. The molecular mechanisms underlying LMNA cardiomyopathy are poorly understood because the interaction between the signaling pathways is challenging to elucidate. Deciphering these pathways is key to understanding the underlying mechanisms of disease and finding novel targets to alter the pathways and lessen the symptoms of diseases.

Perspectives on polarity - exploring biological asymmetry across scales.

In this Perspective, Journal of Cell Science invited researchers working on cell and tissue polarity to share their thoughts on unique, emerging or open questions relating to their field. The goal of this article is to feature 'voices' from scientists around the world and at various career stages, to bring attention to innovative and thought-provoking topics of interest to the cell biology community. These voices discuss intriguing questions that consider polarity across scales, evolution, development and disease. What can yeast and protists tell us about the evolution of cell and tissue polarity in animals? How are cell fate and development influenced by emerging dynamics in cell polarity? What can we learn from atypical and extreme polarity systems? How can we arrive at a more unified biophysical understanding of polarity? Taken together, these pieces demonstrate the broad relevance of the fascinating phenomenon of cell polarization to diverse fundamental biological questions.

A Mammalian-Based Synthetic Biology Toolbox to Engineer Membrane-Membrane Interfaces.

Intercellular membrane-membrane interfaces are compartments with specialized functions and unique biophysical properties that are essential in numerous cellular processes including cell signaling, development, and immunity. Using synthetic biology to engineer or to create novel cellular functions in the intercellular regions has led to an increasing need for a platform that allows generation of functionalized intercellular membrane-membrane interfaces. Here, we present a synthetic biology platform to engineer functional membrane-membrane interfaces using a pair of dimerizing proteins in both cell-free and cellular environments. We envisage this platform to be a helpful tool for synthetic biologists who wish to engineer novel intercellular signaling and communication systems.

Mechanobiology of Dental Pulp Cells.

The dental pulp is the inner part of the tooth responsible for properly functioning during its lifespan. Apart from the very big biological heterogeneity of dental cells, tooth microenvironments differ a lot in the context of mechanical properties-ranging from 5.5 kPa for dental pulp to around 100 GPa for dentin and enamel. This physical heterogeneity and complexity plays a key role in tooth physiology and in turn, is a great target for a variety of therapeutic approaches. First of all, physical mechanisms are crucial for the pain propagation process from the tooth surface to the nerves inside the dental pulp. On the other hand, the modulation of the physical environment affects the functioning of dental pulp cells and thus is important for regenerative medicine. In the present review, we describe the physiological significance of biomechanical processes in the physiology and pathology of dental pulp. Moreover, we couple those phenomena with recent advances in the fields of bioengineering and pharmacology aiming to control the functioning of dental pulp cells, reduce pain, and enhance the differentiation of dental cells into desired lineages. The reviewed literature shows great progress in the topic of bioengineering of dental pulp-although mainly in vitro. Apart from a few positions, it leaves a gap for necessary filling with studies providing the mechanisms of the mechanical control of dental pulp functioning in vivo.