Formation of vimentin biomolecular condensate-like structures under oxidative stress DOI Creative Commons

Paula Martínez-Cenalmor,

Alma E. Martínez, Diego Moneo-Corcuera

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 23, 2024

Abstract The intermediate filament protein vimentin performs a key role in cytoskeletal interplay and dynamics, cellular responses to stress. monomer possesses central α-helical rod domain flanked by N- C-terminal low complexity domains. Interactions between this type of domains play an important function the formation phase-separated biomolecular condensates, which turn are critical for organization components. Vimentin filaments undergo distinct versatile reorganizations response diverse stimuli. Here we show that certain oxidants electrophiles, including hydrogen peroxide diamide, elicit remodeling into small particles. Diamide particular, induces fast conversion circular, motile dots, presence single cysteine residue, C328, is critical. This effect reversible, reassembly can be noticed within minutes removal oxidant. Diamide-elicited structures recover fluorescence after photobleaching. Moreover, fusion cells expressing differentially tagged allows detection dots positive both tags, suggesting merge upon cell fusion. aliphatic alcohol 1,6-hexanediol, known alter interactions domains, readily dissolves diamide-elicited at concentrations, whereas high concentrations it disrupts filaments. Taken together, these results indicate oxidation promote reversible condensate-like structures. hypothesize reorganization droplet-like could protective against irreversible damage oxidative

Language: Английский

Oxidative stress elicits the remodeling of vimentin filaments into biomolecular condensates DOI Creative Commons

Paula Martínez-Cenalmor,

Alma E. Martínez, Diego Moneo-Corcuera

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103282 - 103282

Published: July 24, 2024

The intermediate filament protein vimentin performs an essential role in cytoskeletal interplay and dynamics, mechanosensing cellular stress responses. In pathology, is a key player tumorigenesis, fibrosis infection. Vimentin filaments undergo distinct versatile reorganizations, behave as redox sensors. monomer possesses central α-helical rod domain flanked by N- C-terminal low complexity domains. Interactions between this type of domains play important function the formation phase-separated biomolecular condensates, which turn are critical for organization components. Here we show that several oxidants, including hydrogen peroxide diamide, elicit remodeling into small particles. Oxidative elicited diamide induces fast dissociation circular, motile dots, requires presence single cysteine residue, C328. This effect reversible, reassembly can occur within minutes oxidant removal. Diamide-elicited droplets recover fluorescence after photobleaching. Moreover, fusion cells expressing differentially tagged allows detection dots positive both tags, indicating merge upon cell fusion. aliphatic alcohol 1,6-hexanediol, known to alter interactions domains, readily dissolves diamide-elicited at concentrations, C328 dependent manner, hampers reassembly. Taken together, these results indicate oxidation promotes reversible condensate-like structures, provide primary evidence its regulated phase separation. hypothesize droplet transition could protective against irreversible damage network oxidative stress.

Language: Английский

Citations

6
Anomalous diffusion of active Brownian particles in responsive elastic gels: Nonergodicity, non-Gaussianity, and distributions of trapping times DOI
Koushik Goswami, Andrey G. Cherstvy, Aljaž Godec

et al.

Physical review. E, Journal Year: 2024, Volume and Issue: 110(4)

Published: Oct. 29, 2024

Understanding actual transport mechanisms of self-propelled particles (SPPs) in complex elastic gels---such as the cell cytoplasm, vitro networks chromatin or F-actin fibers, mucus gels---has far-reaching consequences. Implications beyond biology/biophysics are engineering and medicine, with a particular focus on microrheology targeted drug delivery. Here, we examine via extensive computer simulations dynamics SPPs deformable gellike structures responsive to thermal fluctuations. We treat tracer comparable larger than mesh size gel. observe distinct trapping events active tracers at relatively short times, leading subdiffusion; it is followed by an escape from meshwork-induced traps due flexibility network, resulting superdiffusion. thus find crossovers between different regimes. also pronounced nonergodicity non-Gaussianity intermediate times. The distributions times escaping ``cages'' our quasiperiodic gel often reveal existence two timescales dynamics. At high activity these become comparable. Furthermore, that mean waiting time exhibits power-law dependence (in terms their P\'eclet number). Our results additionally showcase both exponential nonexponential activities. Extensions this setup possible, factors such anisotropy particles, topologies various interactions (also nonlocal nature) be considered.

Language: Английский

Citations

5
On‐Origami Molecular Crowding Control of G‐Quadruplex DNAzymes DOI Open Access
Bei Yang, Rujie Wang, Weiying Li

et al.

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Abstract The proper crowding of biomacromolecules in cytoplasm and on cell surfaces plays a critical role morphology metabolism regulations. It is also important to optimize the target molecules at optimal density artificial interfaces perform best activities, which remains challenge. Here, DNA origami employed as precise template regulate placing model DNAzyme, G‐quadruplex (G4)‐hemin complex, achieving high catalytic efficiency moderate crowding. As increases, DNAzyme susceptible inactivation, leading decrease performance. location template, shown be an isotropic scaffold can constructed form nanoenzyme ensembles with variable efficiencies under moderately crowded conditions. G4‐hemin are utilized design mechanochemical sensor accomplish detection disease Human Papillomavirus (HPV)‐16 fragment.

Language: Английский

Citations

0
Liposome-Encapsulated Escherichia coli Lysates to Reconstitute Intracellular Macromolecular Crowding Effects DOI Creative Commons

Milara Kalacheva,

Nuno R. da Silva, Arnold J. Boersma

et al.

ACS Synthetic Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Intracellular macromolecular crowding impacts biomacromolecule behavior, including oligomerization, phase separation, and diffusion. However, understanding effects in cells is challenging as respond adapt to perturbations. Therefore, replicating in-cell liposomes would provide a good alternative studying the consequences of crowding. Here, we achieve physiological levels using Escherichia coli lysates liposomes, verified with sensor. We shrink gradient-wise osmotic upshift reach high effects. see that lysate induces higher than BSA at same mg/mL, showing need use replicate behavior. study small cosolutes on sugars ATP modulate crowding, implying they also affect cells. These artificial display E. 220-300 mg/mL HEK293T 50-100 lysate. Hence, these are platform for obtaining information physiologically relevant controlled environment.

Language: Английский

Citations

0
Targeting Bacterial Cell Division with Benzodioxane–Benzamide FtsZ Inhibitors as a Novel Strategy to Fight Gram-Positive Ovococcal Pathogens DOI Open Access
Berenice Furlan, Marta Sobrinos‐Sanguino,

Maria T. Sammartino

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 714 - 714

Published: Jan. 16, 2025

The widespread emergence of antimicrobial resistance (AMR) is a serious threat to global public health and among Gram-positive cocci, Streptococcus pneumoniae constitutes priority in the list AMR-threatening pathogens. To counteract this fundamental problem, bacterial cell division cycle crucial proteins involved process emerged as novel attractive targets. FtsZ an essential protein, inhibitors, especially benzamide derivatives, have been exploited last decade. In work, we identified, for first time, some benzodioxane-benzamide inhibitors capable targeting pneumoniae, addition their previously demonstrated activity against other bacteria. These promising benzamides, with minimal inhibitory concentrations (MICs) ranging from 25 80 µg/mL, bactericidal S. pneumoniae. This was evidenced by ability dramatically affect growth viability, further supported morphological changes observed through microscopy. Moreover, compounds were characterized vitro, combining turbidity measurements confocal imaging, significant alteration GTP-induced assembly found, line our previous data microorganisms.

Language: Английский

Citations

0
Liquid-liquid phase separation of intrinsically disordered proteins: Effect of osmolytes and crowders DOI

G Priyanka,

E Jawahar Raj,

N. Prakash Prabhu

et al.

Progress in molecular biology and translational science, Journal Year: 2025, Volume and Issue: unknown, P. 249 - 269

Published: Jan. 1, 2025

Language: Английский

Citations

0
60 Years of Studies into the Initiation of Chromosome Replication in Bacteria DOI Creative Commons
John H. Herrick, Victor Norris, Masamichi Kohiyama

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 203 - 203

Published: Feb. 1, 2025

The Replicon Theory has guided the way experiments into DNA replication have been designed and interpreted for 60 years. As part of related, explanatory package guiding experiments, it is thought that timing cell cycle depends in some on a critical mass initiation, Mi, as licensed by variety macromolecules molecules reflecting state cell. To help re-interpretation this data, we focus mainly roles DnaA, RNA polymerase, SeqA, ribonucleotide reductase context "nucleotypic effect".

Language: Английский

Citations

0
Transformative insights in breast cancer: review of atomic force microscopy applications DOI Creative Commons

Jiamin Ma,

Yuanyuan Zhai,

Xiaoyi Ren

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 28, 2025

Breast cancer remains one of the foremost global health concerns, highlighting urgent need for innovative diagnostic and therapeutic strategies. Traditional imaging techniques, such as mammography ultrasound, play essential roles in clinical practice; however, they often fall short detecting early-stage tumors providing comprehensive insights into mechanical properties cells. In this context, Atomic Force Microscopy (AFM) has emerged a transformative tool breast research, owing to its high-resolution capabilities nanomechanical characterization. This review explores recent advancements AFM technology applied emphasizing key findings that include differentiation various stages tumor progression through imaging, precise characterization properties, capability single-cell analysis. These not only enhance our understanding heterogeneity but also reveal potential biomarkers early detection targets. Furthermore, critically examines several challenges limitations associated with application research. Issues complexities sample preparation, accessibility, cost are discussed. Despite these challenges, transform biology is significant. Looking ahead, continued promise deepen guide strategies aimed at improving patient outcomes.

Language: Английский

Citations

0
An Overview of Liquid-Liquid Phase Separation and Its Mechanisms in Sepsis DOI Creative Commons
Meiling Cao, Xinyi Zhang, Xiaohan Wang

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3969 - 3980

Published: March 1, 2025

Sepsis is a systemic inflammatory response syndrome triggered by the invasion of bacteria or pathogenic microorganisms into human body, which may lead to variety serious complications and pose threat patient's life health. Liquid-liquid phase separation (LLPS) biomolecular process in different biomolecules, such as proteins nucleic acids, form liquid condensates through interactions, these play key roles cellular physiological processes. LLPS affect development sepsis several pathways, modulation factors, immune responses, cell death, altering function activity which, turn, infection inflammation. In this paper, we first discuss mechanism separation, then summarize studies sepsis, finally propose potential application treatment strategies, while pointing out limitations existing directions for future research.

Language: Английский

Citations

0
Bifunctional macromolecular design for dual interface-passivating regulation towards practical stable lithium-sulfur batteries DOI
Mengyu Li,

Bobo Zou,

Yan Yu

et al.

Journal of Energy Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0