Search Results (36)

The actomyosin complex—nature’s dynamic engine composed of actin filaments and myosin motors—is emerging as a versatile tool for bio-integrated nanotechnology. This review explores the growing potential of actomyosin-powered systems in biosensing and actuation applications, highlighting their compatibility with physiological conditions, responsiveness to biochemical and physical cues and modular adaptability. We begin with a comparative overview of natural and synthetic nanomachines, positioning actomyosin as a uniquely scalable and biocompatible platform. We then discuss experimental advances in controlling actomyosin activity through ATP, calcium, heat, light and electric fields, as well as their integration into in vitro motility assays, soft robotics and neural interface systems. Emphasis is placed on longstanding efforts to harness actomyosin as a biosensing element—capable of converting chemical or environmental signals into measurable mechanical or electrical outputs that can be used to provide valuable clinical and basic science information such as functional consequences of disease-associated genetic variants in cardiovascular genes. We also highlight engineering challenges such as stability, spatial control and upscaling, and examine speculative future directions, including emotion-responsive nanodevices. By bridging cell biology and bioengineering, actomyosin-based systems offer promising avenues for real-time sensing, diagnostics and therapeutic feedback in next-generation biosensors. Full article

The blood–brain barrier (BBB) comprises distinct cell types, including endothelial cells, pericytes, and astrocytes, and is essential for central nervous system (CNS) homeostasis by selectively regulating molecular transport and maintaining integrity. In particular, astrocytes are essential for BBB function, as they maintain BBB integrity through their end-feet, which form a physical and biochemical interface that enhances endothelial cell function and barrier selectivity. Moreover, they secrete growth factors like vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β), which regulate tight junction (TJ) proteins (e.g., claudins and occludins) crucial for limiting paracellular permeability. Molecular motors like kinesins, dynein, and myosins are essential for these astrocyte functions. By facilitating vesicular trafficking and protein transport, they are essential for various functions, including trafficking of junctional proteins to support BBB integrity, the proper mitochondria localization within astrocyte processes for efficient energy supply, the polarized distribution of aquaporin (AQP)-4 at astrocyte end-feet for regulating water homeostasis across the BBB, and the modulation of neuroinflammatory responses. Moreover, myosin motors modulate actomyosin dynamics to regulate astrocyte process outgrowth, adhesion, migration, and morphology, facilitating their functional roles. Thus, motor protein dysregulation in astrocytes can compromise BBB function and integrity, increasing the risk of neurodegeneration. This review explores the complex interplay between astrocytes and molecular motors in regulating BBB homeostasis, which represents an attractive but poorly explored area of research. Full article

Hypertrophic cardiomyopathy (HCM) is a heterogeneous group of heart muscle disorders that affects millions, with an incidence from 1 in 500 to 1 in 200. Factors such as genetics, age, gender, comorbidities, and environmental factors may contribute to the course of this disease. Diagnosis of HCM has improved significantly in the past few decades from simple echocardiographic evaluations to a more complex, multimodal approach embracing advanced imaging, genetic, and biomarker studies. This review focuses on Mavacamten, a selective allosteric inhibitor of cardiac myosin, as a pharmacological treatment for HCM. Patients with HCM experience pathological actomyosin interactions, leading to impaired relaxation and increased energy expenditure. Mavacamten decreases available myosin heads, reducing actomyosin cross-bridges during systole and diastole. By reducing the number of bridges left ventricular outflow tract pressure is normalized and cardiac cavities are filled. This mechanism enhances patient performance and alleviates symptoms such as chest pain and dyspnea. The results suggest the potential for Mavacamten to transform the treatment of obstructive hypertrophic cardiomyopathy. Studies to date have shown significant improvement in exercise capacity, symptom relief, and a reduction in the need for invasive procedures such as septal myectomy. Further studies are needed to confirm the clinical results. Full article

Myofibrillar proteins primarily consist of myosin, actin, myogenin, and actomyosin. These proteins form complex networks within muscle fibers and are crucial to the physical and chemical properties of meat. Additionally, myofibrillar proteins serve as significant substrates for the adsorption of volatile flavor compounds, including aldehydes, alcohols, ketones, and sulfur and nitrogen compounds, which contribute to the overall flavor profile of meat products. A series of chemical reactions occur during the processing, storage, and transportation of meat products. Oxidation is one of the most significant reactions. Oxidative modification can alter the physical and chemical properties of proteins, ultimately impacting the sensory quality of meat products, including flavor, taste, and color. In recent years, considerable attention has been focused on the effects of protein oxidation on meat quality and its regulation. This study investigates the impact of myofibrillar protein oxidation on the sensory attributes of meat products by analyzing the oxidation processes and the factors that initiate myofibrillar protein oxidation. Additionally, it explores the control of myofibrillar protein oxidation and its implications on the sensory properties of meat products, providing theoretical insights relevant to meat processing methods and quality control procedures. Full article

Eukaryotic cells must accurately transfer their genetic material and cellular components to their daughter cells. Initially, cells duplicate their chromosomes and subsequently segregate them toward the poles. The actomyosin ring, a crucial molecular machinery normally located in the middle of the cells and underneath the plasma membrane, then physically divides the cytoplasm and all components into two daughter cells, each ready to start a new cell cycle. This process, known as cytokinesis, is conserved throughout evolution. Defects in cytokinesis can lead to the generation of genetically unstable tetraploid cells, potentially initiating uncontrolled proliferation and cancer. This review focuses on the molecular mechanisms by which budding yeast cells build the actomyosin ring and the preceding steps involved in forming a scaffolding structure that supports the challenging structural changes throughout cytokinesis. Additionally, we describe how cells coordinate actomyosin ring contraction, plasma membrane ingression, and extracellular matrix deposition to successfully complete cytokinesis. Furthermore, the review discusses the regulatory roles of Cyclin-Dependent Kinase (Cdk1) and the Mitotic Exit Network (MEN) in ensuring the precise timing and execution of cytokinesis. Understanding these processes in yeast provides insights into the fundamental aspects of cell division and its implications for human health. Full article

Non-muscle myosin IIA (NM IIA) is a motor protein that belongs to the myosin II family. The myosin heavy chain 9 (MYH9) gene encodes the heavy chain of NM IIA. NM IIA is a hexamer and contains three pairs of peptides, which include the dimer of heavy chains, essential light chains, and regulatory light chains. NM IIA is a part of the actomyosin complex that generates mechanical force and tension to carry out essential cellular functions, including adhesion, cytokinesis, migration, and the maintenance of cell shape and polarity. These functions are regulated via light and heavy chain phosphorylation at different amino acid residues. Apart from physiological functions, NM IIA is also linked to the development of cancer and genetic and neurological disorders. MYH9 gene mutations result in the development of several autosomal dominant disorders, such as May-Hegglin anomaly (MHA) and Epstein syndrome (EPS). Multiple studies have reported NM IIA as a tumor suppressor in melanoma and head and neck squamous cell carcinoma; however, studies also indicate that NM IIA is a critical player in promoting tumorigenesis, chemoradiotherapy resistance, and stemness. The ROCK-NM IIA pathway regulates cellular movement and shape via the control of cytoskeletal dynamics. In addition, the ROCK-NM IIA pathway is dysregulated in various solid tumors and leukemia. Currently, there are very few compounds targeting NM IIA, and most of these compounds are still being studied in preclinical models. This review provides comprehensive evidence highlighting the dual role of NM IIA in multiple cancer types and summarizes the signaling networks involved in tumorigenesis. Furthermore, we also discuss the role of NM IIA as a potential therapeutic target with a focus on the ROCK-NM IIA pathway. Full article

Actin, which plays a crucial role in cellular structure and function, interacts with various binding proteins, notably myosin. In mammals, actin is composed of six isoforms that exhibit high levels of sequence conservation and structural similarity overall. As a result, the selection of actin isoforms was considered unimportant in structural studies of their binding with myosin. However, recent high-resolution structural research discovered subtle structural differences in the N-terminus of actin isoforms, suggesting the possibility that each actin isoform may engage in specific interactions with myosin isoforms. In this study, we aimed to explore this possibility, particularly by understanding the influence of different actin isoforms on the interaction with myosin 7A. First, we compared the reported actomyosin structures utilizing the same type of actin isoforms as the high-resolution filamentous skeletal α-actin (3.5 Å) structure elucidated using cryo-EM. Through this comparison, we confirmed that the diversity of myosin isoforms leads to differences in interaction with the actin N-terminus, and that loop 2 of the myosin actin-binding sites directly interacts with the actin N-terminus. Subsequently, with the aid of multiple sequence alignment, we observed significant variations in the length of loop 2 across different myosin isoforms. We predicted that these length differences in loop 2 would likely result in structural variations that would affect the interaction with the actin N-terminus. For myosin 7A, loop 2 was found to be very short, and protein complex predictions using skeletal α-actin confirmed an interaction between loop 2 and the actin N-terminus. The prediction indicated that the positively charged residues present in loop 2 electrostatically interact with the acidic patch residues D24 and D25 of actin subdomain 1, whereas interaction with the actin N-terminus beyond this was not observed. Additionally, analyses of the actomyosin-7A prediction models generated using various actin isoforms consistently yielded the same results regardless of the type of actin isoform employed. The results of this study suggest that the subtle structural differences in the N-terminus of actin isoforms are unlikely to influence the binding structure with short loop 2 myosin 7A. Our findings are expected to provide a deeper understanding for future high-resolution structural binding studies of actin and myosin. Full article

Coatomer Protein Complex-II (COPII) mediates anterograde vesicle transport from the endoplasmic reticulum (ER) to the Golgi apparatus. Here, we report that the COPII coatomer complex is constructed dependent on a small GTPase, Sar1, in spermatocytes before and during Drosophila male meiosis. COPII-containing foci co-localized with transitional endoplasmic reticulum (tER)-Golgi units. They showed dynamic distribution along astral microtubules and accumulated around the spindle pole, but they were not localized on the cleavage furrow (CF) sites. The depletion of the four COPII coatomer subunits, Sec16, or Sar1 that regulate COPII assembly resulted in multinucleated cell production after meiosis, suggesting that cytokinesis failed in both or either of the meiotic divisions. Although contractile actomyosin and anilloseptin rings were formed once plasma membrane ingression was initiated, they were frequently removed from the plasma membrane during furrowing. We explored the factors conveyed toward the CF sites in the membrane via COPII-mediated vesicles. DE-cadherin-containing vesicles were formed depending on Sar1 and were accumulated in the cleavage sites. Furthermore, COPII depletion inhibited de novo plasma membrane insertion. These findings suggest that COPII vesicles supply the factors essential for the anchoring and/or constriction of the contractile rings at cleavage sites during male meiosis in Drosophila. Full article

Myosin, a superfamily of motor proteins, obtain the energy they require for movement from ATP hydrolysis to perform various functions by binding to actin filaments. Extensive studies have clarified the diverse functions performed by the different isoforms of myosin. However, the unavailability of resolved structures has made it difficult to understand the way in which their mechanochemical cycle and structural diversity give rise to distinct functional properties. With this study, we seek to further our understanding of the structural organization of the myosin 7A motor domain by modeling the tertiary structure of myosin 7A based on its primary sequence. Multiple sequence alignment and a comparison of the models of different myosin isoforms and myosin 7A not only enabled us to identify highly conserved nucleotide binding sites but also to predict actin binding sites. In addition, the actomyosin-7A complex was predicted from the protein–protein interaction model, from which the core interface sites of actin and the myosin 7A motor domain were defined. Finally, sequence alignment and the comparison of models were used to suggest the possibility of a pliant region existing between the converter domain and lever arm of myosin 7A. The results of this study provide insights into the structure of myosin 7A that could serve as a framework for higher resolution studies in future. Full article

The integrity and permeability of epithelial and endothelial barriers depend on the formation of tight junctions, adherens junctions, and a junction-associated cytoskeleton. The establishment of this junction–cytoskeletal module relies on the correct folding and oligomerization of its protein components. Molecular chaperones are known regulators of protein folding and complex formation in different cellular compartments. Mammalian cells possess an elaborate chaperone network consisting of several hundred chaperones and co-chaperones. Only a small part of this network has been linked, however, to the regulation of intercellular adhesions, and the systematic analysis of chaperone functions at epithelial and endothelial barriers is lacking. This review describes the functions and mechanisms of the chaperone-assisted regulation of intercellular junctions. The major focus of this review is on heat shock protein chaperones, their co-chaperones, and chaperonins since these molecules are the focus of the majority of the articles published on the chaperone-mediated control of tissue barriers. This review discusses the roles of chaperones in the regulation of the steady-state integrity of epithelial and vascular barriers as well as the disruption of these barriers by pathogenic factors and extracellular stressors. Since cytoskeletal coupling is essential for junctional integrity and remodeling, chaperone-assisted assembly of the actomyosin cytoskeleton is also discussed. Full article

Cytokinesis, as the last stage of the cell division cycle, is a tightly controlled process amongst all eukaryotes, with defective division leading to severe cellular consequences and implicated in serious human diseases and conditions such as cancer. Both mammalian cells and the fission yeast Schizosaccharomyces pombe use binary fission to divide into two equally sized daughter cells. Similar to mammalian cells, in S. pombe, cytokinetic division is driven by the assembly of an actomyosin contractile ring (ACR) at the cell equator between the two cell tips. The ACR is composed of a complex network of membrane scaffold proteins, actin filaments, myosin motors and other cytokinesis regulators. The contraction of the ACR leads to the formation of a cleavage furrow which is severed by the endosomal sorting complex required for transport (ESCRT) proteins, leading to the final cell separation during the last stage of cytokinesis, the abscission. This review describes recent findings defining the two phases of cytokinesis in S. pombe: ACR assembly and constriction, and their coordination with septation. In summary, we provide an overview of the current understanding of the mechanisms regulating ACR-mediated cytokinesis in S. pombe and emphasize a potential role of ESCRT proteins in this process. Full article

B cell antigen receptor (BCR) signaling induces actin cytoskeleton remodeling by stimulating actin severing, actin polymerization, and the nucleation of branched actin networks via the Arp2/3 complex. This enables B cells to spread on antigen-bearing surfaces in order to increase antigen encounters and to form an immune synapse (IS) when interacting with antigen-presenting cells (APCs). Although the WASp, N-WASp, and WAVE nucleation-promoting factors activate the Arp2/3 complex, the role of WAVE2 in B cells has not been directly assessed. We now show that both WAVE2 and the Arp2/3 complex localize to the peripheral ring of branched F-actin when B cells spread on immobilized anti-Ig antibodies. The siRNA-mediated depletion of WAVE2 reduced and delayed B cell spreading on immobilized anti-Ig, and this was associated with a thinner peripheral F-actin ring and reduced actin retrograde flow compared to control cells. Depleting WAVE2 also impaired integrin-mediated B cell spreading on fibronectin and the LFA-1-induced formation of actomyosin arcs. Actin retrograde flow amplifies BCR signaling at the IS, and we found that depleting WAVE2 reduced microcluster-based BCR signaling and signal amplification at the IS, as well as B cell activation in response to antigen-bearing cells. Hence, WAVE2 contributes to multiple actin-dependent processes in B lymphocytes. Full article

Cardiac muscle contraction is regulated via Ca²⁺ exchange with the hetero-trimeric troponin complex located on the thin filament. Binding of Ca²⁺ to cardiac troponin C, a Ca²⁺ sensing subunit within the troponin complex, results in a series of conformational re-arrangements among the thin filament components, leading to an increase in the formation of actomyosin cross-bridges and muscle contraction. Ultimately, a decline in intracellular Ca²⁺ leads to the dissociation of Ca²⁺ from troponin C, inhibiting cross-bridge cycling and initiating muscle relaxation. Therefore, troponin C plays a crucial role in the regulation of cardiac muscle contraction and relaxation. Naturally occurring and engineered mutations in troponin C can lead to altered interactions among components of the thin filament and to aberrant Ca²⁺ binding and exchange with the thin filament. Mutations in troponin C have been associated with various forms of cardiac disease, including hypertrophic, restrictive, dilated, and left ventricular noncompaction cardiomyopathies. Despite progress made to date, more information from human studies, biophysical characterizations, and animal models is required for a clearer understanding of disease drivers that lead to cardiomyopathies. The unique use of engineered cardiac troponin C with the L48Q mutation that had been thoroughly characterized and genetically introduced into mouse myocardium clearly demonstrates that Ca²⁺ sensitization in and of itself should not necessarily be considered a disease driver. This opens the door for small molecule and protein engineering strategies to help boost impaired systolic function. On the other hand, the engineered troponin C mutants (I61Q and D73N), genetically introduced into mouse myocardium, demonstrate that Ca²⁺ desensitization under basal conditions may be a driving factor for dilated cardiomyopathy. In addition to enhancing our knowledge of molecular mechanisms that trigger hypertrophy, dilation, morbidity, and mortality, these cardiomyopathy mouse models could be used to test novel treatment strategies for cardiovascular diseases. In this review, we will discuss (1) the various ways mutations in cardiac troponin C might lead to disease; (2) relevant data on mutations in cardiac troponin C linked to human disease, and (3) all currently existing mouse models containing cardiac troponin C mutations (disease-associated and engineered). Full article

Cells of the cardiovascular system are physiologically exposed to a variety of mechanical forces fundamental for both cardiac development and functions. In this context, forces generated by actomyosin networks and those transmitted through focal adhesion (FA) complexes represent the key regulators of cellular behaviors in terms of cytoskeleton dynamism, cell adhesion, migration, differentiation, and tissue organization. In this study, we investigated the involvement of FAs on cardiomyocyte differentiation. In particular, vinculin and focal adhesion kinase (FAK) family, which are known to be involved in cardiac differentiation, were studied. Results revealed that differentiation conditions induce an upregulation of both FAK-Tyr397 and vinculin, resulting also in the translocation to the cell membrane. Moreover, the role of mechanical stress in contractile phenotype expression was investigated by applying a uniaxial mechanical stretching (5% substrate deformation, 1 Hz frequency). Morphological evaluation revealed that the cell shape showed a spindle shape and reoriented following the stretching direction. Substrate deformation resulted also in modification of the length and the number of vinculin-positive FAs. We can, therefore, suggest that mechanotransductive pathways, activated through FAs, are highly involved in cardiomyocyte differentiation, thus confirming their role during cytoskeleton rearrangement and cardiac myofilament maturation. Full article

Formation and maintenance of tissue barriers require the coordination of cell mechanics and cell–cell junction assembly. Here, we combined methods to modulate ECM stiffness and to measure mechanical forces on adhesion complexes to investigate how tight junctions regulate cell mechanics and epithelial morphogenesis. We found that depletion of the tight junction adaptor ZO-1 disrupted junction assembly and morphogenesis in an ECM stiffness-dependent manner and led to a stiffness-dependant reorganisation of active myosin. Both junction formation and morphogenesis were rescued by inhibition of actomyosin contractility. ZO-1 depletion also impacted mechanical tension at cell-matrix and E-cadherin-based cell–cell adhesions. The effect on E-cadherin also depended on ECM stiffness and correlated with effects of ECM stiffness on actin cytoskeleton organisation. However, ZO-1 knockout also revealed tension-independent functions of ZO-1. ZO-1-deficient cells could assemble functional barriers at low tension, but their tight junctions remained corrupted with strongly reduced and discontinuous recruitment of junctional components. Our results thus reveal that reciprocal regulation between ZO-1 and cell mechanics controls tight junction assembly and epithelial morphogenesis, and that, in a second, tension-independent step, ZO-1 is required to assemble morphologically and structurally fully assembled and functionally normal tight junctions. Full article