ArticleProceedings of the National Academy of Sciences of the United States of America2015
Alpha-actinin binding kinetics modulate cellular dynamics and force generation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
58 citing papers in PubMed, 104 citations in OpenAlex.
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- The PDLIM family of actin-associated proteins and their emerging role in membrane trafficking.Biochemical Society transactions · 2023Review
- Cardiomyocyte external mechanical unloading activates modifications of α-actinin differently from sarcomere-originated unloading.The FEBS journal · 2023Article
- HIV Infection: Shaping the Complex, Dynamic, and Interconnected Network of the Cytoskeleton.International journal of molecular sciences · 2023Review
- Systematic altering of semiflexible DNA-based polymer networksNanoscale · 2023Article
- Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers.iScience · 2023Article
- Chlamydia trachomatis Subverts Alpha-Actinins To Stabilize Its Inclusion.Microbiology spectrum · 2023Article
- α-Actinin-4 recruits Shp2 into focal adhesions to potentiate ROCK2 activation in podocytes.Life science alliance · 2022Article
- Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness.iScience · 2022Article
- Vimentin intermediate filaments and filamentous actin form unexpected interpenetrating networks that redefine the cell cortex.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- SERPINE1 Gene Is a Reliable Molecular Marker for the Early Diagnosis of Aortic Dissection.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- α-Actinin1 promotes tumorigenesis and epithelial-mesenchymal transition of gastric cancer via the AKT/GSK3β/β-Catenin pathway.Bioengineered · 2021Article
- A designer cell culture insert with a nanofibrous membrane toward engineering an epithelial tissue model validated by cellular nanomechanics.Nanoscale advances · 2021Article
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- Subtle changes in crosslinking drive diverse anomalous transport characteristics in actin-microtubule networks.Soft matter · 2021Article
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6 authors at 1 institution in 2 countries.
Funding
Abstract
The actin cytoskeleton is a key element of cell structure and movement whose properties are determined by a host of accessory proteins. Actin cross-linking proteins create a connected network from individual actin filaments, and though the mechanical effects of cross-linker binding affinity on actin networks have been investigated in reconstituted systems, their impact on cellular forces is unknown. Here we show that the binding affinity of the actin cross-linker α-actinin 4 (ACTN4) in cells modulates cytoplasmic mobility, cellular movement, and traction forces. Using fluorescence recovery after photobleaching, we show that an ACTN4 mutation that causes human kidney disease roughly triples the wild-type binding affinity of ACTN4 to F-actin in cells, increasing the dissociation time from 29 ± 13 to 86 ± 29 s. This increased affinity creates a less dynamic cytoplasm, as demonstrated by reduced intracellular microsphere movement, and an approximate halving of cell speed. Surprisingly, these less motile cells generate larger forces. Using traction force microscopy, we show that increased binding affinity of ACTN4 increases the average contractile stress (from 1.8 ± 0.7 to 4.7 ± 0.5 kPa), and the average strain energy (0.4 ± 0.2 to 2.1 ± 0.4 pJ). We speculate that these changes may be explained by an increased solid-like nature of the cytoskeleton, where myosin activity is more partitioned into tension and less is dissipated through filament sliding. These findings demonstrate the impact of cross-linker point mutations on cell dynamics and forces, and suggest mechanisms by which such physical defects lead to human disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.