Nuclear pore permeability and fluid flow are modulated by its dilation state DOI Creative Commons
Patrick C. Hoffmann, Hyuntae Kim, Agnieszka Obarska-Kosińska

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Changing environmental conditions necessitate rapid adaptation of cytoplasmic and nuclear volumes. We use the slime mold Dictyostelium discoideum, known for its ability to tolerate extreme changes in osmolarity, assess which role pore complexes (NPCs) play achieving volume relieving mechanical stress. capitalize on unique properties D. discoideum quantify fluid flow across NPCs. has an elaborate NPC structure situ. Its dilation state affects permeability nucleocytosolic flow. Based mathematical concepts adapted from hydrodynamics, we conceptualize this phenomenon as porous NPCs, is distinct canonically characterized modes nucleocytoplasmic transport because dependence pressure. Viral blockage decreased Our results may be relevant any biological that entail size adaptation, including metastasizing cancer cells, migrating or differentiating tissues.

Language: Английский

Osmosis-driven stiffening of structured hydrogels DOI Creative Commons
Ran Zhao,

Alexandra Thoma,

Esther Amstad

et al.

Applied Materials Today, Journal Year: 2024, Volume and Issue: 37, P. 102155 - 102155

Published: March 12, 2024

Plant cells harness osmotic pressures to stiffen their leaves through strong turgor pressures. Key this osmosis-driven stiffening is the confinement of liquids within semipermeable membranes that can regulate transport water molecules and ions. Inspired by effect in plants, we fabricate rather stiff hydrogels with inclusions fill them polyelectrolytes possessing a high degree swelling. The swelling these spatially confined stiffer inert hydrogel surrounding, resulting an up three-fold increase stiffness structured compared matrix water-filled inclusions. We leverage pressure gradients change morphology cm-sized immersing bottom parts water, without need for additional stimuli consume energy or require environmental conditions. Similarly, exploit release ball. foresee materials open new possibilities actuate soft benign, energy-efficient manner.

Language: Английский

Citations

3
The Erosion of Healthcare and Scientific Integrity: A Growing Concern DOI Creative Commons
Björn L.D.M. Brücher

Journal of Healthcare Leadership, Journal Year: 2025, Volume and Issue: Volume 17, P. 23 - 43

Published: Feb. 1, 2025

Tremendous achievements in healthcare and science over the past 200 years have enhanced life expectancy parallel with a shift from dogma to humanistic liberal education. Advancements cancer included vaccines treating causes of (eg, hepatitis C- induced liver human papillomavirus-induced cervical cancer) along improved survival children. In contrast, developments cancer, frequently touted as "discoveries" or "breakthroughs" media headlines, been demonstrated be ephemeral rather than game changers. reality, incidences are increasing, relapse mortality rates not changed substantially. By this, we experiencing today similar challenges those before so-called Humboldt reform. The trend towards managerialism focus on quantity health care endangers their integrity. Due complexity integrity science, in-depth contemplation this review contains foundations actions information regarding an example, healthcare, technology, publishing, marketing media, predatory publishers, followed by psychologic sociologic aspects which influence our perception. A complex paradoxical transformation has occurred, quality humanism replaced quantity, revenue, marketing, together "citation silence", (ignoring original findings), increased corruption misconduct. This explains why is being eroded. Countries societies only strong both emphasis Awareness situation may represent first step toward renewed accountability.

Language: Английский

Citations

0
Indocyanine Green Aggregation-Induced Hypotonic Stress to Remodel Aloe Exosome-like Vesicles for Enhanced Tumor Penetration and Phototherapy DOI

Lupeng Zeng,

Wanhua Shi,

Kewen Chen

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

As ubiquitous transport nanovesicles in cell biology, plant exosome-like vesicles (PELVs) have enormous potential to deliver drugs safely and effectively. Drug encapsulation mechanical stability of are key limitations influencing their delivery efficiency. However, common methods (i.e., ultrasound, electroporation) for drug loading inevitably affect the inherent vesicle characteristics, which influence stability, leakproof nature, cellular internalization, tumor penetration. Herein, order balance this contradiction, we put forward a strategy skillfully remodel aloe (AELVs) through indocyanine green (ICG)-induced hypotonic stress during endogenous loading. We observe that rigidity AELVs is enhanced with accumulation long hydrocarbon chain lipids under ICG-induced stress. Synchronously, ICG also loaded into (ICG/AELVs, IAs), effectively prevents secondary damage More interestingly, find promotes IA secretion less intravesicular protein, beneficial enlarge inner space more The IAs show great storage leakproof, antidegradation performance. Compared control AELVs, higher liable penetrate tumor. further modifying AS1411 aptamer (AS1411-IAs, AIAs) exhibit high targeting vivo. After intravenous administration, 4T1 obviously inhibited by AIAs plus NIR irradiation, improves survival rate tumor-bearing mice. Overall, systematically explore effects drug-induced osmotic on PELVs achieve efficient therapy. This work simplifies process enhances plasticity, provides promising perspective PELV-based clinical application.

Language: Английский

Citations

0
Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization DOI Creative Commons

Ting‐Ching Wang,

Samere Abolghasemzade,

B. McKee

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 22, 2024

Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate expression through YAP localization. We investigated the role of lamina in this process. show exhibits mechanical threshold behavior: once unwrinkled, is inextensible. A computational model predicts unwrinkled under tension, which confirmed using a lamin tension sensor. Laminar unwrinkling caused flattening during spreading on stiff ECM. Knockdown A/C eliminates surface and decreases These findings cells conforms to drop reveal for controlling localization cells. Matrix induced regulates This study finds induces promotes yes associated protein (YAP), transcriptional co-activator.

Language: Английский

Citations

3
Nuclear pore permeability and fluid flow are modulated by its dilation state DOI Creative Commons
Patrick C. Hoffmann, Hyuntae Kim, Agnieszka Obarska-Kosińska

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Changing environmental conditions necessitate rapid adaptation of cytoplasmic and nuclear volumes. We use the slime mold Dictyostelium discoideum, known for its ability to tolerate extreme changes in osmolarity, assess which role pore complexes (NPCs) play achieving volume relieving mechanical stress. capitalize on unique properties D. discoideum quantify fluid flow across NPCs. has an elaborate NPC structure situ. Its dilation state affects permeability nucleocytosolic flow. Based mathematical concepts adapted from hydrodynamics, we conceptualize this phenomenon as porous NPCs, is distinct canonically characterized modes nucleocytoplasmic transport because dependence pressure. Viral blockage decreased Our results may be relevant any biological that entail size adaptation, including metastasizing cancer cells, migrating or differentiating tissues.

Language: Английский

Citations

3