Bone biomineralization is a tightly regulated process mediated by osteogenic proteins associated with extracellular vesicles known as matrix vesicles (MVs), which function as specialized nanoreactors for the nucleation and propagation of biological apatite. The activity of MV-associated proteins, including tissue-nonspecific alkaline phosphatase (TNAP), nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1), PHOSPHO1, and annexins, is strongly influenced by the physicochemical properties of the vesicular membrane. Membrane composition, lipid packing, phase behavior, surface charge, and lipid microdomains regulate protein localization, conformation, catalytic activity, and intermolecular interactions, thereby controlling mineral formation. However, the structural complexity and heterogeneity of native MVs have hindered a detailed mechanistic understanding of protein–lipid interactions during biomineralization. This review examines the biophysical principles governing lipid membrane organization and their influence on the function of membrane-associated osteogenic proteins. Emphasis is placed on biomimetic membrane systems, including liposomes, proteoliposomes, giant unilamellar vesicles, Langmuir monolayers, and Langmuir–Blodgett films, which provide simplified and controllable platforms for investigating protein–lipid interactions and membrane-mediated mineralization. We also summarize key techniques for characterizing native vesicles and biomimetic membranes, including atomic force microscopy, confocal and electron microscopy, dynamic light scattering, nanoparticle tracking analysis, flow cytometry, Fourier-transform infrared and Raman spectroscopy, and boron-doped diamond microelectrodes. Finally, advanced and complementary approaches such as surface plasmon resonance, small-angle X-ray scattering, and microfluidic platforms are highlighted for their potential to advance the molecular understanding of membrane-associated biomineralization. Collectively, these complementary models and analytical methods provide an integrated framework for elucidating matrix vesicle function and guiding the rational design of biomaterials and vesicle-inspired therapeutic strategies for bone regeneration.
The 2027 Special Issue of Biophysical Reviews: “Vietnam Biophysics—Current Status, Challenges, and Future Opportunities” highlights the rapid growth of biophysics research in the Vietnamese Biophysical Society and its expanding contributions to the global scientific community. We invite Review and Commentary articles covering recent advances in structural, molecular, and computational biophysics, biophotonics, nanobiophysics, AI-driven biophysics, and applications in medicine, agriculture, food, and environmental sciences. This collection aims to showcase interdisciplinary innovation while providing perspectives on future opportunities for biophysics research in Vietnam.
Antimicrobial peptides (AMPs) interact with lipid membranes through multistep processes that may include interfacial adsorption, partial insertion, membrane deformation, pore formation, and transmembrane organization. Although these processes have been extensively investigated, a unified operational framework connecting surface-bound, inserted, and intermediate peptide–membrane states remains underdeveloped. Here, we present a regime-based field-coupling framework that organizes peptide–membrane interactions according to the relative predominance of interfacial electrostatic coupling, hydrophobic-core coupling, and mixed coupling contributions. Surface-bound states are characterized primarily by interactions between cationic peptide residues and anionic lipid headgroups, whereas inserted states display stronger engagement of nonpolar peptide surfaces with lipid acyl chains. Mixed and pore-associated states retain both polar and hydrophobic interactions and may additionally involve water penetration, lipid-headgroup reorientation, membrane thinning, curvature, and peptide oligomerization. The operational use of the framework integrates peptide charge and charge distribution, hydrophobic moment, length and topology, membrane anionic charge, acyl-chain saturation, bilayer thickness, and peptide concentration. These variables are related to coordinated computational and experimental observables, including insertion depth, peptide–headgroup contacts, nonpolar residue–acyl-chain contacts, anionic lipid enrichment, peptide orientation, membrane order, water penetration, deformation, and peptide–peptide association. The framework generates conditional and falsifiable predictions for surface-bound, inserted/core, carpet-like, barrel-stave, and mixed/toroidal regimes. Its application to representative peptide–membrane systems illustrates how published observations can be organized within a common operational map. The proposed framework remains qualitative, and quantitative boundaries between coupling regimes require validation across peptides and membranes with distinct physicochemical properties. Nevertheless, it provides a structured basis for comparing mechanisms, designing computational and experimental tests, and interpreting transitions among peptide–membrane interaction states.
Modern biophysics has evolved from the measurement of isolated molecular properties toward increasingly integrated molecular characterization. Advances in instrumentation, orthogonal workflows, and multidimensional analytical platforms have expanded the breadth of molecular information obtainable from a single experimental context, increasing what we define here as “information density”. In this review, we examine the scientific and technological forces underlying this transition and propose state-centric biophysics as an interpretive framework in which biophysical properties like affinity, kinetics, thermodynamics, stability, structural dynamics, hydrodynamics, ligand occupancy, and assembly state are viewed as complementary descriptors of a shared molecular-state landscape rather than as independent experimental outputs. Representative case studies, including targeted protein degradation, molecular glues, Heat Shock Protein 90 (HSP90) molecular cycle and inhibition, and state-selective inhibition of Kirsten Rat Sarcoma Viral Oncogene Homolog G12C (KRAS G12C), illustrate how biological activity frequently depends on molecular-state properties that extend beyond ligand occupancy alone. Collectively, these observations suggest that the central challenge of modern biophysics is increasingly shifting from measuring molecular properties to identifying the molecular states that govern mechanism, efficacy, selectivity, and therapeutic response.
Protein-based therapeutics have become an important part of modern medicine, offering highly specific and effective treatments for a wide range of diseases and improving patients’ quality of life compared with many conventional small-molecule drugs. Owing to their macromolecular nature, the successful administration of these agents has consistently faced significant challenges. The rapid advancement of nanotechnology in recent decades has encouraged the development of innovative and cost-effective nanostructured systems designed to improve protein stability, protection, and targeted delivery. Direct observation of underlying phenomena at the subatomic scale between nanostructures and proteins is usually not feasible in experimental setups; in this context, molecular modeling techniques such as molecular dynamics (MD) have paved the way for revealing the molecular mechanisms governing protein-nanostructure interactions and stability. In this review, we summarize recent computational studies on protein-nanostructure interactions with different classes of nanomaterials, including biocompatible polymers (chitosan, PLGA), inorganic nanoparticles (AuNPs, ZnONPs), and carbon-based materials (SWCNTs, C60). These investigations demonstrate that MD simulations can explain mechanisms of adsorption, encapsulation, conformational stability, structural change, and protein corona formation, thus supporting the rational design of improved nanocarriers. Despite the growing interest in nanomedicine, MD investigations of lipid-based nanostructures remain relatively limited, even though these systems are widely used in pharmaceutical formulations. We further discuss the important factors affecting the accuracy and predictive capability of MD simulations, including force field selection, system representation, simulation timescale, and molecular resolution. Future progress needs transferable parameters, improved pH-dependent modeling, and the integration of multiscale simulation methods to capture complex phenomena like protein corona formation.
ATP-dependent chromatin remodelers use a conserved Snf2-family ATPase motor to generate diverse remodeling outcomes in distinct chromatin contexts. From cumulative work across several years, autoinhibition is emerging as one mechanism that explains such specificity. Family-specific inhibitory domains or accessory modules restrain the ATPase motor until the appropriate nucleosomal cues are encountered. These cues include histone tails, linker DNA, the acidic patch, or, in specialized contexts, damage-induced PARylation. We discuss how this principle operates in ISWI, CHD, ALC1, and INO80-family remodelers, where distinct regulatory elements couple substrate recognition to productive remodeling. Together, these studies emphasize that chromatin remodelers are not constitutively active motors that are merely recruited to chromatin, but context-sensitive molecular machines whose activity is gated by information encoded within the nucleosome itself.
This editorial describes an open the call for nominations to the 2027 Michéle Auger Award for Young Scientists’ Independent Research—the single award administered by Biophysical Reviews.
The history behind the proof, and acceptance, of neutral lipid domains in the plasma membranes of transformed and cancer cells is noteworthy. Not only for the controversy, but because this membrane structure has become a hallmark for women at risk for breast cancer. The membrane model, proposed in 1988 to contain isotropically tumbling domains, made up of triglycerides, cholesterol, and cholesterol ester, was not verified until 2010 by a team of Danish scientists. In the intervening 22 years, focus in this area was on the fluid lipid bilayer and the presence of intracellular droplets. The proof of neutral lipid domains in the plasma membranes, mobile on the MR timescale, involved chemists, physicists, pathologists, and surgeons from Australia and Canada and finally Denmark. Today, the appearance of these neutral lipid domains is the first of a series of changes that are diagnostic for risk of breast cancer and considered by some as a point of clinical pharmaceutical intervention for those at risk of developing cancer.
Cardiomyocyte function emerges from tightly coupled electromechanical processes that span sarcomeric force generation, titin-based elasticity, excitation–contraction coupling, mitochondrial ATP supply, and mechanotransductive adaptation to load. Insulin signaling integrates these processes across molecular, cellular, and organ scales, thereby contributing to cardiomyocyte mechanical homeostasis. In cardiomyocytes, canonical insulin signaling is initiated by insulin receptor (IR) activation, recruitment of IRS-1/IRS-2, and downstream PI3K–Akt signaling. Through Akt-dependent modulation of mTOR, GSK-3β, and FOXO transcription factors, insulin aligns energy availability with mechanical demand while supporting structural integrity of sarcomeres, Z-disc/costameric networks, and intercalated disc architecture. Disruption of insulin signaling and insulin resistance in type 2 diabetes (T2DM) remodel cardiomyocyte mechanics by altering myofilament calcium sensitivity, shifting contractile protein expression, perturbing titin isoform composition and phosphorylation, impairing calcium cycling and β-adrenergic microdomain signaling, and inducing mitochondrial dysfunction with oxidative stress (Fig. 1). These changes manifest as altered force–pCa relations, reduced contractile reserve, prolonged relaxation, increased passive stiffness, and modified viscoelastic behavior, as measured by quantitative biophysical assays (Fig. 2). Here, we synthesize mechanistic pathways linking insulin signaling to cardiac mechanics; summarize evidence for T2DM-induced cardiomyocyte dysfunction across species and disease stages; describe mechanotransduction failure in diabetes involving costameres, integrins/FAK, and stretch-responsive pathways such as YAP/TAZ; and provide an overview of quantitative tools to measure cardiomyocyte mechanics including AFM, TFM, nanoindentation, optical/magnetic tweezers, skinned-cell mechanics, real-time calcium–contractility platforms, engineered heart tissues, and microphysiological heart-on-chip systems. Finally, we discuss therapeutic perspectives with emphasis on interventions that restore mechanical homeostasis through titin phosphorylation, reduction of AGE-driven stiffening, and normalization of oxidative and inflammatory stress, including SGLT2 inhibitors and GLP-1 agonists.
This review analyzes recent advances and future perspectives on the use of clathrate hydrates in medicine. Data on cryopreservation of biological tissues, gas-mediated anesthetic mechanisms, antimicrobial technologies, imaging applications, and selected drug-delivery-related examples are systematized. Special attention is given to the critical analysis of methodological limitations of existing studies and the barriers to clinical implementation. Despite the promising nature of fundamental research, translation into clinical practice still requires overcoming major technological and methodological obstacles. The review also highlights the need to distinguish hydrate-specific effects from those of dissolved gas and ultra-fine bubbles, as this mechanistic ambiguity remains a major limitation in several biomedical contexts.
Hypertrophic cardiomyopathy (HCM) has long been viewed as the archetypal monogenic disorder caused by pathogenic variants in the genes encoding components of the sarcomere. However, the fact that only one-third of HCM cases are genotype-positive, as well as other factors such as incomplete disease penetrance and marked phenotypic heterogeneity, challenge this reductionist view. Recent advances in mass spectrometry-based proteomics have provided new opportunities to interrogate human HCM myocardium at unprecedented depth and are reshaping our understanding of HCM pathobiology. In this mini-review, we summarize insights from both top-down and bottom-up proteomics studies showing that HCM is characterized by broad molecular remodeling across multiple cellular compartments, including the sarcomere, sarcoplasmic reticulum, cytoskeleton, mitochondria, and nucleus. Together, these studies support a model in which diverse HCM genotypes converge on shared downstream proteomic phenotypes and highlight proteomics as a powerful approach for defining disease mechanisms, modifiers, and therapeutic targets.
This is a call for papers for a special issue of Biophysical Reviews devoted to Biomolecular Condensates in Living Systems. Our objective is to have under one volume a selection of articles that can give the wider scientific community a firm insight into current developments in the dynamic and rapidly evolving field of biomolecular condensates.
Myosin light chain kinase (MLCK) serves as a central, phosphorylation-dependent molecular switch that governs myosin activation and muscle contractility. Upon binding Ca2⁺/calmodulin, it phosphorylates the regulatory light chain (RLC) of myosin, inducing conformational transitions that shift myosin from an inhibited, folded state to an extended, force-generating configuration. MLCK is a ubiquitous kinase that phosphorylates both striated and non-striated myosin, albeit through distinct regulatory mechanisms. While the structural transition from inhibited to activated myosin and the contraction-initiation pathway are well established, structural details of MLCK activation and its precise interactions remain incompletely resolved due to the absence of a high-resolution structure of full-length MLCK. Recent advances in structural biology, including cryo-electron microscopy, have significantly expanded our understanding of myosin and MLCK dynamics. However, critical challenges remain, particularly in visualizing the molecular architecture of MLCK and conformational transitions underlying myosin activation. This review integrates current knowledge of the structural and mechanistic basis of myosin regulation by MLCK, emphasizing conformational switching, phosphorylation-dependent activation, and most importantly, its unique way of functioning in the striated and non-striated muscle systems. Understanding these molecular processes will provide critical insights into muscle contractility and its implications in disease states linked to myosin activation.
Myosins are actin-based molecular motors that power diverse forms of cellular motility across life. Initially characterized as the contractile machinery of muscle, the superfamily now includes numerous non-muscle classes with distinct cellular functions. Over the past decades, work across numerous actin-based systems has uncovered multiple modes of non-muscle myosin control. Recent advances now expand and, in some cases, challenge conventional regulatory paradigms, underscoring the complexity and adaptability of myosin function in cellular contexts. In this short review, I begin with a concise summary of the major canonical regulatory systems for non-muscle myosins. I follow this by highlighting the major novel regulatory findings from the last decade specifically relating to protein-binding partner activation, structural lipid-binding motifs, co-assembly of mixed classes of myosins, and the regulation of multi-motor complexes by the nanoscale organization of cellular actin. This review will appeal to the general scientific reader aiming to understand the mechanisms regulating myosins outside of the context of muscle and the current state of the non-muscle myosin field.
The contractile apparatus of striated muscle, including both skeletal and cardiac muscle, intrinsically exhibits self-sustained oscillatory behavior under intermediate activation states between contraction and relaxation. This phenomenon, termed SPOC (spontaneous oscillatory contraction), provides unique insights into the dynamic regulation of force generation. In this review, we first highlight experimental findings that characterize SPOC and then focus on theoretical frameworks developed to capture its essential features. A key feature of these models is the assumption that the lattice spacing, that is, the distance between the thick and thin filaments, varies dynamically during muscle contraction and that actomyosin activity depends on this spacing. This assumption naturally explains the emergence of SPOC. Particular attention is given to models constructed for single sarcomeres, isolated myofibrils, and small bundles of myofibrils, through which the underlying mechanisms of SPOC can be systematically understood. Finally, by extending the mathematical structure of these models, we propose that SPOC may exhibit chaotic properties, thereby providing a comprehensive understanding of its mechanisms and physiological significance.
The beating of the heart is driven by sliding between myosin-containing thick filaments and actin-containing thin filaments and at the single-molecule level by the ‘powerstroke’ in the lever arm of the myosin head, which tilts while its catalytic domain is attached to actin. This tilting lever-arm paradigm was developed before the molecular structure of the thick filament had been determined, and excluded the interactions between the myosin heads and the thick filaments that are now known to stabilise an OFF state of myosin. Here we re-examine the paradigm using measurements of the orientation of two components of the lever arm, the N- and C-lobes of the myosin regulatory light chain (RLC) in heart muscle cells by fluorescence for in situ structure (FISS), comparing them with those in cryo-electron microscopy (cryo-EM) structures of myosin fragments and of the C zone of thick filaments in the OFF state. We show that these FISS and cryo-EM results, combined with those of other structural studies on myosin fragments and muscle cells, can be explained by a modified tilting lever-arm paradigm that includes interactions between the myosin heads and the thick filament during the contractile cycle. In the new model, one head of each myosin dimer remains docked on the surface of the thick filament while its partner ‘working’ head executes the powerstroke and hydrolyses ATP. The interaction between the docked and working heads of the dimer both primes the working head to attach to an appropriate actin monomer in the pre-powerstroke state and re-captures the working head into the dimer after it has hydrolysed ATP.
Large conductance voltage- and Ca2⁺-activated K⁺ (BK) channels are key regulators of membrane excitability and intracellular Ca2⁺ signaling in a wide range of excitable and non-excitable cells. Although the biophysical properties of BK channels have been extensively characterized, it has become increasingly clear that their functional diversity arises largely from interactions with a broad network of associated proteins. In this focused review, we provide an updated overview of the BK channel protein interactome, highlighting how these interactions shape channel gating, trafficking, localization, and coupling to Ca2⁺ sources. We discuss well-established regulatory partners, including β and γ auxiliary subunits, as well as emerging modulators such as BKIP-1 and LINGO-1. We further examine interactions with cytoskeletal and trafficking proteins that govern BK channel surface expression and mobility, and with Ca2⁺-permeable channels and receptors, including voltage-gated Ca2⁺ channels, TRP channels, ryanodine receptors, IP₃ receptors, and NMDA receptors, that create specialized Ca2⁺ signaling nanodomains. Finally, we summarize the roles of intracellular signaling molecules and scaffolding proteins that integrate BK channels into larger signaling assemblies. Together, these findings position BK channels as central hubs within multiprotein complexes that enable precise, context-dependent control of cellular excitability and Ca2⁺-dependent physiological processes.
