A5070394629- Cellular Mechanics and Interactions
- Nuclear Structure and Function
- Hippo pathway signaling and YAP/TAZ
- Microfluidic and Bio-sensing Technologies
- Force Microscopy Techniques and Applications
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- Wnt/β-catenin signaling in development and cancer
- Tissue Engineering and Regenerative Medicine
- Additive Manufacturing and 3D Printing Technologies
- Blood properties and coagulation
- Spaceflight effects on biology
McGill University
2019-2024
Yes-associated protein (YAP) is a key mechanotransduction in diverse physiological and pathological processes; however, ubiquitous YAP activity regulatory mechanism living cells has remained elusive. Here, we show that nuclear translocation highly dynamic during cell movement driven by compression arising from contractile work. We resolve the mechanistic role of cytoskeletal contractility manipulation mechanics. Disrupting linker nucleoskeleton cytoskeleton complex reduces for given...
While diverse cellular components have been identified as mechanotransduction elements, the deformation of nucleus itself is a critical mechanosensory mechanism, implying that nuclear stiffness essential in determining responses to intracellular and extracellular stresses. Although membrane protein lamin A/C known contribute stiffness, bulk moduli nuclei not reported for various levels A/C. Here, we measure function expression applied osmotic stress, revealing linear dependence within range...
Summary YAP is a key mechanotransduction protein with essential roles in diverse physiological processes. Dysregulation activity associated multiple diseases such as atherosclerosis, fibrosis, and cancer progression. Here we examine the physical stimuli that regulate dynamic translocation to nucleus. Through combination of biophysical studies, demonstrate localization insensitive cell substrate stiffness, but strongly determined by cellular contractile work, which turn deforms We show...
3D culture platforms with tunable stiffness have the potential to improve many applications, such as drug discovery, organoid studies, and stem cell differentiation. Both dimensionality regulate crucial relevant cellular processes. However, models are often limited in throughput difficult adopt for widespread use. Here, we demonstrate an accessible 3D, stiffness-tunable tissue platform, based on interpenetrating network of collagen-1 alginate. When blended polymers that induce phase...
The sensing and generation of cellular forces are essential aspects life. Traction force microscopy (TFM) has emerged as a standard broadly applicable methodology to measure cell contractility its role in behavior. While TFM platforms have enabled diverse discoveries, their implementation remains limited part due various constraints, such time-consuming substrate fabrication techniques, the need detach cells null images, followed by complex imaging analysis, unavailability for...
The role of morphogenetic forces in cell fate specification is an area intense interest. Our prior studies suggested that the development high cell-cell tension human embryonic stem cells (hESC) colonies permits Src-mediated phosphorylation junctional β-catenin accelerates its release to potentiate Wnt-dependent signaling critical for initiating mesoderm specification. Using ectopically expressed nonphosphorylatable mutant (Y654F), we now provide direct evidence impeding tension-dependent...
The role of morphogenetic forces in cell fate specification is an area intense interest. Our prior studies suggested that the development high cell-cell tension human embryonic stem cells (hESC) colonies permits Src-mediated phosphorylation junctional β-catenin accelerates its release to potentiate Wnt-dependent signaling critical for initiating mesoderm specification. Using ectopically expressed nonphosphorylatable mutant (Y654F), we now provide direct evidence impeding tension-dependent...
Abstract The nucleus is the largest organelle and information center of cell; while diverse cellular components have been identified as mechanotransduction elements, deformation itself emerging a critical mechanosensory mechanism, suggesting that nuclear stiffness essential in determining responses to intracellular extracellular stresses. membrane protein, lamin A, known be dominant component stiffening; however, quantitative relationship between A expression still unclear. Here we measure...
Abstract The sensing and generation of cellular forces are essential aspects life. Traction Force Microscopy (TFM) has emerged as a standard broadly applicable methodology to measure cell contractility its role in behavior. While TFM platforms have enabled diverse discoveries, their implementation remains limited part due various constraints, such time-consuming substrate fabrication techniques, the need detach cells null force images, followed by complex imaging analysis, unavailability for...