Biophysical reviews最新文献

This systematic review consolidates current research on mineralizing extracellular vesicles, or matrix vesicles (MVs), including their isolation, characterization, and role in physiological and pathological calcification. We searched PubMed/Medline, Scopus, and Web of Knowledge by employing the keywords "matrix vesicles" or "collagenase-released matrix vesicles" or "mineralizing vesicles" and publishing years from 2000 to 2023. Seventy-one studies met the inclusion criteria. The studies described different experimental protocols, especially with respect to methods for isolating MVs, wherein digestion with collagenase combined with centrifugation was the most used. The studies employed characterization techniques, including the determination of alkaline phosphatase (ALP) and transmission electron microscopy (TEM), to assess the functionality, size, and morphology of MVs. MVs contain key proteins such as ALP, annexins, and osteocalcin, along with calcium and phosphate ions, which are all critical for precipitating apatite. In the studies, evaluation of ALP activity revealed that MVs are more effective for mineralization than their parent cells and, hence, a valuable tool to regenerate bone and to engineer tissues. On the other hand, MVs play an essential role in pathologies, and the studies showed how they contribute to vascular calcification. Despite the therapeutic potential of MVs, isolation methods and characterization protocols vary across the studies, so standardized methods are needed. We have consolidated the data resulting from this systematic review in an open digital library on MVs with free access to all researchers. The users of the digital library can apply filters and taxonomy to find and interconnect the data resulting from the review.

Many enzymes operate through mechanisms that comply with the Michaelis-Menten equation (hyperbolic kinetics). The theoretical framework for analyzing these enzymes, widely developed in the literature, is largely based on the ability to linearize the equation and apply linear regression to experimental data. However, certain systems, such as P-type ATPases, present mechanisms that do not fit into hyperbolic models, requiring the development of more complex equations. This study explores the underlying causes of the non-hyperbolic behavior observed for P-type ATPases and reviews some methodologies used for their analysis. Here, we propose to employ rational equations, whose form limits the range of possible kinetic models applicable to the system, offering a structured approach to its analysis.

The kinetics of ligand binding to ferric heme proteins is relevant in a variety of biochemical processes. With a few exceptions, ferric heme proteins at physiological pH typically show the sixth (distal) coordination position of the heme iron occupied by a water molecule. This contrasts with ferrous heme proteins, where this position is usually vacant in the absence of external ligands. In this review, we shed light on mechanistic aspects of this process, by discussing our recent results of binding of hydrogen sulfide and hydrosulfide (H₂S/HS^-) and disulfane and hydrodisulfide (HSSH/HSS^-) to ferric microperoxidase 11 (MP11Fe^III) and metmyoglobin (MbFe^III), as well as binding of peroxynitrous acid/peroxynitrite (ONOOH/ONOO^-) to ferric M. tuberculosis nitrobindin (NbFe^III). Stopped flow experimental results of ligand binding rates as a function of pH can be analyzed with a mechanistic proposal consisting of ligand migration and ligand binding steps. Ligand migration to the active site was studied by using steered classical molecular dynamics simulations. The process of ligand binding substitution of the coordinated water molecule has been studied using hybrid quantum-classical (QM-MM) tools. Our results suggest that water molecule release is the critical event of the process in most of the cases, consistently with previous proposals. However, the scenario is complex, since water release depends subtly on the heme environment and may be also assisted by the acid-base behavior of the incoming ligands. Ligand migration may also play a key role in cases in which the active site entrance is hindered.

In this work, we present a brief and concise review about the main features of protein folding which is one of the central research questions at the interface of physics, molecular biology, and computational sciences. We describe the physical foundations of the protein folding phenomenon itself and how it arises as both a free energy minimization process combined with a hydrophobic collapse of the enzyme molten globule due to inter and intramolecular forces among amino acid residues themselves and water molecules. We cover briefly some basic statistical physics-based models to predict the thermodynamic properties of the protein folding transition. Then, we focus our attention on the implementation of computational algorithms designed to minimize energy functions in polypeptides.

Single-molecule magnetic tweezers have recently emerged as a powerful technique for measuring the equilibrium dynamics of individual proteins under force. In magnetic tweezers, a single protein is tethered between a glass coverslip and a superparamagnetic bead, and by applying and controlling a magnetic field, the protein is mechanically stretched while force-induced conformational changes are measured by tracking the vertical position of the bead. The soft trap created by the magnetic field provides intrinsic force-clamp conditions, which makes magnetic tweezers particularly well-suited to measure protein conformational dynamics. Traditionally employed to study DNA due to their initially low spatial and temporal resolutions, magnetic tweezers instrumentation has experienced significant progress in recent years. The development of high-speed cameras, stronger illumination sources, advanced image analysis algorithms, and dedicated chemical functionalization strategies, now allow for high-resolution and ultra-stable experiments. Together with their ability to apply and control low forces, magnetic tweezers can capture long-term equilibrium protein folding dynamics, not possible with any other technique. These capabilities have proven particularly valuable in the study of force-sensing protein systems, which often exhibit low mechanical stabilities that are challenging to measure with other techniques. In this review, we will discuss the current status of magnetic tweezers instrumentation for studying protein folding dynamics, focusing on both the instrumental aspects and methodologies to interpret nanomechanical experiments.

We present a transcript of the Phase Space Invaders podcast interview, with Tamar Schlick interviewed by Miłosz Wieczór. The conversation covers topics in computational biophysics and beyond: DNA and RNA research from genome organization to viral RNA frameshifting, transitioning from applied math to biology, developing algorithms and their utility in molecular dynamics and complex multiscale systems, the role of computers in biophysical research, writing reviews and books, collaborating in science, and using long-distance running as a template for building supportive communities.

We announce call for papers for a Special Issue of Biophysical Reviews associated with the Russian Autumn School in Biophysics held in Kazan, Russia, 11-14 November 2024. The autumn school was focused on modern biophysical methods and approaches to study living and model biological systems. It was the most important biophysical meeting within 2024 in Russia, organized for the first time with perspectives to make it regular. The Special Issue accepts reviews on comprehensive analysis of experimental and computational methods currently used to study the dynamical structure of biological systems at all levels of living matter organization-from submolecular, molecular and supramolecular model systems to cells and whole organisms. Here, we describe main themes and sections, types of papers and key dates for the journal issue.

Solar radiation is predominantly Earth's natural ultraviolet (UV) radiation source. The biological effects of UV radiation have been the subject of scientific interest for decades. The most frequent and abundant types of DNA damage comprise the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone (6-4PP) photoproducts. Upon UVA excitation, the 6-4PPs may undergo an intramolecular 4π electrocyclization of the pyrimidone ring, arising photolesions known as Dewar isomers. The photochemistry pathways of UVA/UVB-induced DNA damage are discussed. Photosensitization-mediated reactions have traditionally been categorized as either oxygen-independent or oxygen-dependent. In oxygen-independent processes, the underlying mechanism involves triplet-triplet energy transfer. Among the reactive oxygen species (ROS) generated by UV radiation (¹O₂, O₂ ^•-, ^•OH, H₂O₂), singlet oxygen (¹O₂) is highly reactive and a primary contributor to oxidative DNA damage in cells and human skin following UVA exposure, as observed in the production of 8-oxoguanine (8-OxoG). The exposure of melanocytes to UV radiation upregulates nitric oxide synthase (NOS) and NADPH oxidase (NOX), producing nitric oxide and superoxide, which recombine to produce peroxynitrite. This highly oxidizing species is responsible for melanin chemiexcitation, producing carbonyl products that transfer energy to the DNA molecule to produce CPDs in the dark several hours after UV exposure ends. The peroxynitrite generated could also lead to other types of DNA damage, such as the formation of 8-nitroguanine (8-NitroG), which requires further study.

This review highlights current insights into the regulation of the mitochondrial respiratory chain (electron transport chain, ETC) activity. The regulation of ETC properties optimizes ATP synthesis and controls the generation of the superoxide anion radical (O₂ ^•-) which can be converted into other reactive oxygen species (ROS) playing a dual role by initiating signaling cascades or contributing to oxidative stress. We examine how ETC activity is influenced by the structure and conformation of its complexes, their allosteric or post-translational modifications, and their interactions with membrane lipids. The formation and function of supercomplexes, as well as their cell-type-specific characteristics, are also discussed, alongside with the role of intracellular Ca²⁺ concentration in the modulation of ETC activity. Furthermore, we discuss mechanisms and sites of O₂ ^•- generation within ETC complexes, O₂ ^•- fate in the mitochondrial matrix, and the impact of cytochrome c (Cyt c) conformation and allosteric modifications on ETC function. Finally, we discuss various abnormalities in ETC complexes, emphasizing their relevance to mitochondrial dysfunction and disease.

This commentary is a report by two senior members of the Biophysical Society of Japan (BSJ), who were fortunate enough to be able to attend, on the changes in participant statistics between two IUPAB congresses held in Kyoto in 1978 and 2024. The two tables presented illustrate the changes: one shows the number of participants by region (Asia, Europe, etc.) and the other shows the participation by country. Asia has seen a significant increase in participation, while Europe and the United States have seen a decrease. We examined the factors behind this shift, including the unique characteristics of the BSJ and the Biophysical Society (United States, BPS), advances in transportation and communications, and geopolitical changes affecting Asia and Europe. Finally, we made recommendations for the future direction of the IUPAB.