Investigation of the Role of Stress Fiber Contractility and Nucleus Geometry in the Response of Cells to Micropipette Aspiration

2012 ◽  
Author(s):  
Noel H. Reynolds ◽  
William Ronan ◽  
Enda P. Dowling ◽  
J. Patrick McGarry
Keyword(s):  
Actin Cytoskeleton ◽  
Critical Role ◽  
Stress Fiber ◽  
Micropipette Aspiration ◽  
Mechanical Stimuli ◽  
Cell Cytoplasm

Remodeling of the actin cytoskeleton plays a critical role in the response of cells to mechanical stimuli. Previous studies have investigated the response of cells to micropipette aspiration using passive visco-elastic models for the cell cytoplasm [1–3].

scholarly journals The Role of WAVE2 Signaling in Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1217
Author(s):  
Priyanka Shailendra Rana ◽  
Akram Alkrekshi ◽  
Wei Wang ◽  
Vesna Markovic ◽  
Khalid Sossey-Alaoui
Keyword(s):  
Actin Cytoskeleton ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Critical Role ◽  
Therapeutic Strategies ◽  
Small Gtpases ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Regulatory Complex

The Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE)—WAVE1, WAVE2 and WAVE3 regulate rapid reorganization of cortical actin filaments and have been shown to form a key link between small GTPases and the actin cytoskeleton. Upon receiving upstream signals from Rho-family GTPases, the WASP and WAVE family proteins play a significant role in polymerization of actin cytoskeleton through activation of actin-related protein 2/3 complex (Arp2/3). The Arp2/3 complex, once activated, forms actin-based membrane protrusions essential for cell migration and cancer cell invasion. Thus, by activation of Arp2/3 complex, the WAVE and WASP family proteins, as part of the WAVE regulatory complex (WRC), have been shown to play a critical role in cancer cell invasion and metastasis, drawing significant research interest over recent years. Several studies have highlighted the potential for targeting the genes encoding either part of or a complete protein from the WASP/WAVE family as therapeutic strategies for preventing the invasion and metastasis of cancer cells. WAVE2 is well documented to be associated with the pathogenesis of several human cancers, including lung, liver, pancreatic, prostate, colorectal and breast cancer, as well as other hematologic malignancies. This review focuses mainly on the role of WAVE2 in the development, invasion and metastasis of different types of cancer. This review also summarizes the molecular mechanisms that regulate the activity of WAVE2, as well as those oncogenic pathways that are regulated by WAVE2 to promote the cancer phenotype. Finally, we discuss potential therapeutic strategies that target WAVE2 or the WAVE regulatory complex, aimed at preventing or inhibiting cancer invasion and metastasis.

scholarly journals Shared and Unique Roles of Cap23 and Gap43 in Actin Regulation, Neurite Outgrowth, and Anatomical Plasticity

2000 ◽  
Vol 149 (7) ◽  
pp. 1443-1454 ◽  
Author(s):  
Dunja Frey ◽  
Thorsten Laux ◽  
Lan Xu ◽  
Corinna Schneider ◽  
Pico Caroni
Keyword(s):  
Actin Cytoskeleton ◽  
Neurite Outgrowth ◽  
Critical Role ◽  
Brain Structures ◽  
Calmodulin Binding ◽  
Essentially Normal ◽  
Anatomical Plasticity ◽  
Nerve Sprouting

CAP23 is a major cortical cytoskeleton–associated and calmodulin binding protein that is widely and abundantly expressed during development, maintained in selected brain structures in the adult, and reinduced during nerve regeneration. Overexpression of CAP23 in adult neurons of transgenic mice promotes nerve sprouting, but the role of this protein in process outgrowth was not clear. Here, we show that CAP23 is functionally related to GAP43, and plays a critical role to regulate nerve sprouting and the actin cytoskeleton. Knockout mice lacking CAP23 exhibited a pronounced and complex phenotype, including a defect to produce stimulus-induced nerve sprouting at the adult neuromuscular junction. This sprouting deficit was rescued by transgenic overexpression of either CAP23 or GAP43 in adult motoneurons. Knockin mice expressing GAP43 instead of CAP23 were essentially normal, indicating that, although these proteins do not share homologous sequences, GAP43 can functionally substitute for CAP23 in vivo. Cultured sensory neurons lacking CAP23 exhibited striking alterations in neurite outgrowth that were phenocopied by low doses of cytochalasin D. A detailed analysis of such cultures revealed common and unique functions of CAP23 and GAP43 on the actin cytoskeleton and neurite outgrowth. The results provide compelling experimental evidence for the notion that CAP23 and GAP43 are functionally related intrinsic determinants of anatomical plasticity, and suggest that these proteins function by locally promoting subplasmalemmal actin cytoskeleton accumulation.

scholarly journals Deciphering Nuclear Mechanobiology in Laminopathy

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 231 ◽  
Author(s):  
Jungwon Hah ◽  
Dong-Hwee Kim
Keyword(s):  
Structural Integrity ◽  
Critical Role ◽  
Nuclear Lamina ◽  
Mechanical Stimuli ◽  
Cellular Mechanics ◽  
Know How ◽  
Disease Relevance ◽  
Biochemical Signals ◽  
Nuclear Response

Extracellular mechanical stimuli are translated into biochemical signals inside the cell via mechanotransduction. The nucleus plays a critical role in mechanoregulation, which encompasses mechanosensing and mechanotransduction. The nuclear lamina underlying the inner nuclear membrane not only maintains the structural integrity, but also connects the cytoskeleton to the nuclear envelope. Lamin mutations, therefore, dysregulate the nuclear response, resulting in abnormal mechanoregulations, and ultimately, disease progression. Impaired mechanoregulations even induce malfunction in nuclear positioning, cell migration, mechanosensation, as well as differentiation. To know how to overcome laminopathies, we need to understand the mechanisms of laminopathies in a mechanobiological way. Recently, emerging studies have demonstrated the varying defects from lamin mutation in cellular homeostasis within mechanical surroundings. Therefore, this review summarizes recent findings highlighting the role of lamins, the architecture of nuclear lamina, and their disease relevance in the context of nuclear mechanobiology. We will also provide an overview of the differentiation of cellular mechanics in laminopathy.

Abstract 282: Functional Analysis Of Micrornas In Vascular Disease

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Shusheng Wang ◽  
Qinbo Zhou ◽  
Chastain Anderson
Keyword(s):  
Actin Cytoskeleton ◽  
Therapeutic Potential ◽  
Vascular Development ◽  
Critical Role ◽  
Vascular Diseases ◽  
Tube Formation ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Actin Dynamics

microRNAs (miRNA, miR) are emerging as pivotal modulators of vascular development and disease. Research is my lab is focused on elucidating the functional mechanism and exploring therapeutic potential of microRNAs in vascular diseases. Our recent studies have shown that miR-23 and miR-27 in miR-23~27~24 family are required for proper angiogenesis and neovascularization in a laser-induced vascular injury model. Here we extend our study and provide evidence that miR-24 regulates actin dynamics in ECs through targeting multiple members downstream of Rho signaling, including Pak4, Limk2 and Diaph1 proteins. Consistent with the critical role for actin cytoskeleton in cell motility and proliferation, overexpression of miR-24 in ECs blocks stress fiber and lamellipodia formation, represses EC migration, proliferation and tube formation in vitro, as well as angiogenesis in an ex vivo aortic ring assay. Overexpression of miR-24 in transgenic mice represses postnatal retinal vascular development. Moreover, subretinal delivery of miR-24 mimics represses laser-induced CNV in vivo. Mechanistically, knockdown of miR-24 target protein LIMK2 or PAK4 inhibits stress fiber formation and tube formation in vitro, mimicking miR-24 overexpression phenotype in angiogenesis. Taken together, these findings demonstrate that miR-24 represses angiogenesis by simultaneously regulating multiple components in the actin cytoskeleton pathways, suggesting distinct function of miR-23~27~24 family members in angiogenesis. Manipulation of actin cytoskeleton pathways by miR-24 may represent an attractive therapeutic solution for numerous vascular diseases.

scholarly journals The Aftermath of Bronchoconstriction

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Michael J. O'Sullivan ◽  
Bo Lan
Keyword(s):  
Airway Inflammation ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Airway Remodeling ◽  
Critical Role ◽  
Mechanical Effect ◽  
Mechanical Stimuli ◽  
Underlying Mechanisms ◽  
New Evidence

Asthma is characterized by chronic airway inflammation, airway remodeling, and excessive constriction of the airway. Detailed investigation exploring inflammation and the role of immune cells has revealed a variety of possible mechanisms by which chronic inflammation drives asthma development. However, the underlying mechanisms of asthma pathogenesis still remain poorly understood. New evidence now suggests that mechanical stimuli that arise during bronchoconstriction may play a critical role in asthma development. In this article, we review the mechanical effect of bronchoconstriction and how these mechanical stresses contribute to airway remodeling independent of inflammation.

Dynamics of Stretch-Induced Stress Fiber Remodeling in 3D Cell Culture

2011 ◽  
Author(s):  
Sheng-Lin Lee ◽  
Ali Nekouzadeh ◽  
Kenneth M. Pryse ◽  
Elliot L. Elson ◽  
Guy M. Genin
Keyword(s):  
Cell Culture ◽  
Extracellular Matrix ◽  
Actin Cytoskeleton ◽  
3D Cell Culture ◽  
Living Cells ◽  
Stress Fiber ◽  
Cell Physiology ◽  
Mechanical Stimuli ◽  
Tissue Development ◽  
Induced Stress

The responses of living cells to mechanical stimuli are believed to underlie diseases such as fibrotic cardiomyopathy [1] and asthma [2]. Emerging evidence suggests that mechanical signals transduced through the actin cytoskeleton and its connections to the extracellular matrix (ECM) have important effects on cell physiology and tissue development [13]. Understanding the responses of cells in realistic mechanical environments to mechanical stimuli is therefore of great importance to understanding development and disease.

Quantitative Studies of Endothelial Cell Fibronectin and Filamentous Actin (F-Actin) Coalignment in Response to Shear Stress

2017 ◽  
Vol 23 (5) ◽  
pp. 1013-1023 ◽  
Author(s):  
Xianghui Gong ◽  
Xixi Zhao ◽  
Bin Li ◽  
Yan Sun ◽  
Meili Liu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Actin Cytoskeleton ◽  
Vascular Tissue ◽  
Flow Direction ◽  
Critical Role ◽  
Focal Adhesions ◽  
Mechanical Stimuli ◽  
Cell Alignment ◽  
Filamentous Actin ◽  
Enhancement Method

AbstractBoth fibronectin (FN) and filamentous actin (F-actin) fibers play a critical role for endothelial cells (ECs) in responding to shear stress and modulating cell alignment and functions. FN is dynamically coupled to the F-actin cytoskeleton via focal adhesions. However, it is unclear how ECs cooperatively remodel their subcellular FN matrix and intracellular F-actin cytoskeleton in response to shear stress. Current studies are hampered by the lack of a reliable and sensitive quantification method of FN orientation. In this study, we developed a MATLAB-based feature enhancement method to quantify FN and F-actin orientation. The role of F-actin in FN remodeling was also studied by treating ECs with cytochalasin D. We have demonstrated that FN and F-actin codistributed and coaligned parallel to the flow direction, and that F-actin alignment played an essential role in regulating FN alignment in response to shear stress. Our findings offer insight into how ECs cooperatively remodel their subcellular ECM and intracellular F-actin cytoskeleton in response to mechanical stimuli, and are valuable for vascular tissue engineering.

scholarly journals Tsc1 regulates tight junction independent of mTORC1

2021 ◽  
Vol 118 (30) ◽  
pp. e2020891118
Author(s):  
Mingqiang Lai ◽  
Wenchong Zou ◽  
Zelong Han ◽  
Ling Zhou ◽  
Zeyou Qiu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Tight Junction ◽  
Actin Cytoskeleton ◽  
Critical Role ◽  
Adherens Junction ◽  
Cell Junctions ◽  
Whole Body ◽  
Mechanistic Target Of Rapamycin

Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor that functions together with Tsc2 to negatively regulate the mechanistic target of rapamycin complex 1 (mTORC1) activity. Here, we show that Tsc1 has a critical role in the tight junction (TJ) formation of epithelium, independent of its role in Tsc2 and mTORC1 regulation. When an epithelial cell establishes contact with neighboring cells, Tsc1, but not Tsc2, migrates from the cytoplasm to junctional membranes, in which it binds myosin 6 to anchor the perijunctional actin cytoskeleton to β-catenin and ZO-1. In its absence, perijunctional actin cytoskeleton fails to form. In mice, intestine-specific or inducible, whole-body Tsc1 ablation disrupts adherens junction/TJ structures in intestine or skin epithelia, respectively, causing Crohn’s disease–like symptoms in the intestine or psoriasis-like phenotypes on the skin. In patients with Crohn’s disease or psoriasis, junctional Tsc1 levels in epithelial tissues are markedly reduced, concomitant with the TJ structure impairment, suggesting that Tsc1 deficiency may underlie TJ-related diseases. These findings establish an essential role of Tsc1 in the formation of cell junctions and underpin its association with TJ-related human diseases.

The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

2008 ◽  
Vol 15 (2) ◽  
pp. 50-59 ◽  
Author(s):  
Amy Philofsky
Keyword(s):  
Language Development ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Children With Asd ◽  
Prevalence Estimates ◽  
Notable Increase ◽  
Screening Assessment ◽  
Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

A critical role of iNOS-derived Nitric Oxide (NO) and progesterone in implantation

1998 ◽  
Vol 5 (1) ◽  
pp. 115A-115A
Author(s):  
K CHWALISZ ◽  
E WINTERHAGER ◽  
T THIENEL ◽  
R GARFIELD
Keyword(s):  
Nitric Oxide ◽  
Critical Role
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