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Article ; Online: Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants.

Zhang, Aiwen / Abdellatef, Shimaa A / Nakanishi, Jun

Analytical sciences : the international journal of the Japan Society for Analytical Chemistry

2023 Volume 39, Issue 3, Page(s) 395–405

Abstract: Epidermal growth factor (EGF) gains unique selective cytotoxicity against cancer cells upon conjugation with gold nanoparticles (GNPs). We have previously developed several lysine-free EGF mutants for favorable interactions between the nanoparticle ... ...

Abstract	Epidermal growth factor (EGF) gains unique selective cytotoxicity against cancer cells upon conjugation with gold nanoparticles (GNPs). We have previously developed several lysine-free EGF mutants for favorable interactions between the nanoparticle conjugates with EGF receptor (EGFR) and found one mutant (SR: K28S/K48R) showing stronger anticancer activities. However, the exact mechanisms for the selective cytotoxicity enhancement in the SR mutant remained unsolved. In this study, we analyzed how the nanoparticle conjugates of EGF variants interacted differently with A431 cancer cells, in terms of receptor binding, activation, and trafficking. Our results indicate that the essential feature of the SR-GNP conjugates in the cytotoxicity enhancement is their preferential activation of the clathrin-independent endocytosis pathway. It is suggested that we should focus on not only ligand-receptor binding affinity but also the selectivity of the receptor endocytic route to optimize the anticancer effects in this modality.
MeSH term(s)	Epidermal Growth Factor/metabolism ; Gold ; Endocytosis/physiology ; Metal Nanoparticles ; Clathrin/metabolism
Chemical Substances	Epidermal Growth Factor (62229-50-9) ; Gold (7440-57-5) ; Clathrin
Language	English
Publishing date	2023-01-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1483376-1
ISSN	1348-2246 ; 1348-2246
ISSN (online)	1348-2246
ISSN	1348-2246
DOI	10.1007/s44211-022-00256-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Photoactivatable surfaces resolve the impact of gravity vector on collective cell migratory characteristics.

Sakakibara, Shinya / Abdellatef, Shimaa A / Yamamoto, Shota / Kamimura, Masao / Nakanishi, Jun

Science and technology of advanced materials

2023 Volume 24, Issue 1, Page(s) 2206525

Abstract: Despite considerable interest in the impact of space travel on human health, the influence of the gravity vector on collective cell migration remains unclear. This is primarily because of the difficulty in inducing collective migration, where cell ... ...

Abstract	Despite considerable interest in the impact of space travel on human health, the influence of the gravity vector on collective cell migration remains unclear. This is primarily because of the difficulty in inducing collective migration, where cell clusters appear in an inverted position against gravity, without cellular damage. In this study, photoactivatable surfaces were used to overcome this challenge. Photoactivatable surfaces enable the formation of geometry-controlled cellular clusters and the remote induction of cellular migration via photoirradiation, thereby maintaining the cells in the inverted position. Substrate inversion preserved the circularity of cellular clusters compared to cells in the normal upright position, with less leader cell appearance. Furthermore, the inversion of cells against the gravity vector resulted in the remodeling of the cytoskeletal system via the strengthening of external actin bundles. Within the 3D cluster architecture, enhanced accumulation of active myosin was observed in the upper cell-cell junction, with a flattened apical surface. Depending on the gravity vector, attenuating actomyosin activity correlates with an increase in the number of leader cells, indicating the importance of cell contractility in collective migration phenotypes and cytoskeletal remodeling.
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2027985-1
ISSN	1878-5514 ; 1468-6996
ISSN (online)	1878-5514
ISSN	1468-6996
DOI	10.1080/14686996.2023.2206525
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Article ; Online: Precise Tuning and Characterization of Viscoelastic Interfaces for the Study of Early Epithelial-Mesenchymal Transition Behaviors.

Chang, Alice Chinghsuan / Uto, Koichiro / Abdellatef, Shimaa A / Nakanishi, Jun

Langmuir : the ACS journal of surfaces and colloids

2022 Volume 38, Issue 17, Page(s) 5307–5314

Abstract: There is growing evidence that cellular functions are regulated by the viscoelastic nature of surrounding matrices. This study aimed to investigate the impact of interfacial viscoelasticity on adhesion and epithelial-mesenchymal transition (EMT) ... ...

Abstract	There is growing evidence that cellular functions are regulated by the viscoelastic nature of surrounding matrices. This study aimed to investigate the impact of interfacial viscoelasticity on adhesion and epithelial-mesenchymal transition (EMT) behaviors of epithelial cells. The interfacial viscoelasticity was manipulated using spin-coated thin films composed of copolymers of ε-caprolactone and d,l-lactide photo-cross-linked with benzophenone, whose mechanical properties were characterized using atomic force microscopy and a rheometer. The critical range for the morphological transition of epithelial Madin-Darby canine kidney (MDCK) cells was of the order of 10
MeSH term(s)	Animals ; Dogs ; Elasticity ; Epithelial-Mesenchymal Transition ; Madin Darby Canine Kidney Cells ; Microscopy, Atomic Force ; Viscosity
Language	English
Publishing date	2022-02-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.1c03048
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Article ; Online: Photoactivatable substrates for systematic study of the impact of an extracellular matrix ligand on appearance of leader cells in collective cell migration.

Abdellatef, Shimaa A / Nakanishi, Jun

Biomaterials

2018 Volume 169, Page(s) 72–84

Abstract: Epithelial cells migrate as multicellular units. The directionality and speed of these units are determined by actively moving leader cells. It is important to understand how external cues affect the appearance of these leader cells in physiological and ... ...

Abstract	Epithelial cells migrate as multicellular units. The directionality and speed of these units are determined by actively moving leader cells. It is important to understand how external cues affect the appearance of these leader cells in physiological and pathological processes. However, the impact of extracellular matrices (ECMs) is still controversial, because physically-adsorbed ECM proteins are amenable to protein remodeling, and uncontrolled cluster geometry can vary migration phenotypes. Here, we demonstrate a photoactivatable substrate, which we used to study the impact of a cyclic Arg-Gly-Asp (cRGD) ligand on leader cell formation in MDCK cells. This robust platform allowed us to investigate the effect of cRGD density on leader cell formation, in any given cluster geometry, with minimized ECM remodeling. Our results show a biphasic response of leader cell appearance upon reducing the surface cRGD density. The increase, in leader cell appearance, within the higher density range, is not only associated with the weakening of circumferential actomyosin belts, but also reduction of cellular mechanical tension and intercellular junctional E-cadherin. These results indicate that cRGD-mediated cell-ECM interactions positively regulate mechanical and biochemical coupling within cell clusters; both are critical for the coordination of cell collectives and eventual reduction in the appearance of leader cells.
MeSH term(s)	Animals ; Biocompatible Materials ; Cell Adhesion/drug effects ; Cell Communication/drug effects ; Cell Movement/drug effects ; Dogs ; Extracellular Matrix ; Ligands ; Madin Darby Canine Kidney Cells ; Oligopeptides ; Photosensitizing Agents
Chemical Substances	Biocompatible Materials ; Ligands ; Oligopeptides ; Photosensitizing Agents ; arginyl-glycyl-aspartic acid (78VO7F77PN)
Language	English
Publishing date	2018-03-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2018.03.045
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Article: Photoactivatable substrates for systematic study of the impact of an extracellular matrix ligand on appearance of leader cells in collective cell migration

Abdellatef, Shimaa A / Jun Nakanishi

Biomaterials. 2018 July, v. 169

2018

Abstract	Epithelial cells migrate as multicellular units. The directionality and speed of these units are determined by actively moving leader cells. It is important to understand how external cues affect the appearance of these leader cells in physiological and pathological processes. However, the impact of extracellular matrices (ECMs) is still controversial, because physically-adsorbed ECM proteins are amenable to protein remodeling, and uncontrolled cluster geometry can vary migration phenotypes. Here, we demonstrate a photoactivatable substrate, which we used to study the impact of a cyclic Arg-Gly-Asp (cRGD) ligand on leader cell formation in MDCK cells. This robust platform allowed us to investigate the effect of cRGD density on leader cell formation, in any given cluster geometry, with minimized ECM remodeling. Our results show a biphasic response of leader cell appearance upon reducing the surface cRGD density. The increase, in leader cell appearance, within the higher density range, is not only associated with the weakening of circumferential actomyosin belts, but also reduction of cellular mechanical tension and intercellular junctional E-cadherin. These results indicate that cRGD-mediated cell-ECM interactions positively regulate mechanical and biochemical coupling within cell clusters; both are critical for the coordination of cell collectives and eventual reduction in the appearance of leader cells.
Keywords	cadherins ; cell movement ; epithelial cells ; extracellular matrix ; geometry ; ligands ; phenotype
Language	English
Dates of publication	2018-07
Size	p. 72-84.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2018.03.045
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

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Article: Precise Tuning and Characterization of Viscoelastic Interfaces for the Study of Early Epithelial–Mesenchymal Transition Behaviors

Chang, Alice Chinghsuan / Uto, Koichiro / Abdellatef, Shimaa A. / Nakanishi, Jun

Langmuir. 2022 Feb. 10, v. 38, no. 17

2022

Abstract	There is growing evidence that cellular functions are regulated by the viscoelastic nature of surrounding matrices. This study aimed to investigate the impact of interfacial viscoelasticity on adhesion and epithelial–mesenchymal transition (EMT) behaviors of epithelial cells. The interfacial viscoelasticity was manipulated using spin-coated thin films composed of copolymers of ε-caprolactone and d,l-lactide photo-cross-linked with benzophenone, whose mechanical properties were characterized using atomic force microscopy and a rheometer. The critical range for the morphological transition of epithelial Madin–Darby canine kidney (MDCK) cells was of the order of 10² ms relaxation time, which was 1–2 orders of magnitude smaller than the relaxation times reported (10–10² s). An analysis of strain rate-dependent viscoelastic properties revealed that the difference was caused by the different strain rate/frequency used for the mechanical characterization of the interface and bulk. Furthermore, decoupling of the interfacial viscous and elastic terms demonstrated that E/N-cadherin expression levels were regulated differently by interfacial relaxation and elasticity. These results confirm the significance of precise manipulation and characterization of interfacial viscoelasticity in mechanobiology studies on EMT progression.
Keywords	adhesion ; atomic force microscopy ; benzophenones ; biophysics ; composite polymers ; deformation ; dogs ; epithelium ; kidneys ; mechanical properties ; rheometers ; viscoelasticity
Language	English
Dates of publication	2022-0210
Size	p. 5307-5314.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.1c03048
Database	NAL-Catalogue (AGRICOLA)

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Article: Mapping stress inside living cells by atomic force microscopy in response to environmental stimuli.

Wang, Hongxin / Zhang, Han / Tamura, Ryo / Da, Bo / Abdellatef, Shimaa A / Watanabe, Ikumu / Ishida, Nobuyuki / Fujita, Daisuke / Hanagata, Nobutaka / Nakagawa, Tomoki / Nakanishi, Jun

Science and technology of advanced materials

2023 Volume 24, Issue 1, Page(s) 2265434

Abstract: The response of cells to environmental stimuli, under either physiological or pathological conditions, plays a key role in determining cell fate toward either adaptive survival or controlled death. The efficiency of such a feedback mechanism is closely ... ...

Abstract	The response of cells to environmental stimuli, under either physiological or pathological conditions, plays a key role in determining cell fate toward either adaptive survival or controlled death. The efficiency of such a feedback mechanism is closely related to the most challenging human diseases, including cancer. Since cellular responses are implemented through physical forces exerted on intracellular components, more detailed knowledge of force distribution through modern imaging techniques is needed to ensure a mechanistic understanding of these forces. In this work, we mapped these intracellular forces at a whole-cell scale and with submicron resolution to correlate intracellular force distribution to the cytoskeletal structures. Furthermore, we visualized dynamic mechanical responses of the cells adapting to environmental modulations in situ. Such task was achieved by using an informatics-assisted atomic force microscope (AFM) indentation technique where a key step was Markov-chain Monte Carlo optimization to search for both the models used to fit indentation force-displacement curves and probe geometry descriptors. We demonstrated force dynamics within cytoskeleton, as well as nucleoskeleton in living cells which were subjected to mechanical state modulation: myosin motor inhibition, micro-compression stimulation and geometrical confinement manipulation. Our results highlight the alteration in the intracellular prestress to attenuate environmental stimuli; to involve in cellular survival against mechanical signal-initiated death during cancer growth and metastasis; and to initiate cell migration.
Language	English
Publishing date	2023-10-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2027985-1
ISSN	1878-5514 ; 1468-6996
ISSN (online)	1878-5514
ISSN	1468-6996
DOI	10.1080/14686996.2023.2265434
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Article ; Online: Oscillatory movement of a dynein-microtubule complex crosslinked with DNA origami.

Abdellatef, Shimaa A / Tadakuma, Hisashi / Yan, Kangmin / Fujiwara, Takashi / Fukumoto, Kodai / Kondo, Yuichi / Takazaki, Hiroko / Boudria, Rofia / Yasunaga, Takuo / Higuchi, Hideo / Hirose, Keiko

eLife

2022 Volume 11

Abstract: Bending of cilia and flagella occurs when axonemal dynein molecules on one side of the axoneme produce force and move toward the microtubule (MT) minus end. These dyneins are then pulled back when the axoneme bends in the other direction, meaning ... ...

Abstract	Bending of cilia and flagella occurs when axonemal dynein molecules on one side of the axoneme produce force and move toward the microtubule (MT) minus end. These dyneins are then pulled back when the axoneme bends in the other direction, meaning oscillatory back and forth movement of dynein during repetitive bending of cilia/flagella. There are various factors that may regulate the dynein activity, e.g. the nexin-dynein regulatory complex, radial spokes, and central apparatus. In order to understand the basic mechanism of dynein's oscillatory movement, we constructed a simple model system composed of MTs, outer-arm dyneins, and crosslinks between the MTs made of DNA origami. Electron microscopy (EM) showed pairs of parallel MTs crossbridged by patches of regularly arranged dynein molecules bound in two different orientations, depending on which of the MTs their tails bind to. The oppositely oriented dyneins are expected to produce opposing forces when the pair of MTs have the same polarity. Optical trapping experiments showed that the dynein-MT-DNA-origami complex actually oscillates back and forth after photolysis of caged ATP. Intriguingly, the complex, when held at one end, showed repetitive bending motions. The results show that a simple system composed of ensembles of oppositely oriented dyneins, MTs, and inter-MT crosslinkers, without any additional regulatory structures, has an intrinsic ability to cause oscillation and repetitive bending motions.
MeSH term(s)	Axonemal Dyneins/metabolism ; Axoneme/metabolism ; Chlamydomonas reinhardtii/metabolism ; DNA/metabolism ; Dyneins/metabolism ; Flagella/physiology ; Microtubules/metabolism ; Movement/physiology
Chemical Substances	DNA (9007-49-2) ; Axonemal Dyneins (EC 3.6.4.2) ; Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2022-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.76357
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Article: Hemostatic system and COVID-19 crosstalk: A review of the available evidence.

Wifi, Mohamed-Naguib / Morad, Mohamed Abdelkader / El Sheemy, Reem / Abdeen, Nermeen / Afify, Shimaa / Abdalgaber, Mohammad / Abdellatef, Abeer / Zaghloul, Mariam / Alboraie, Mohamed / El-Kassas, Mohamed

World journal of methodology

2022 Volume 12, Issue 5, Page(s) 331–349

Abstract: Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant coronavirus disease 2019 (COVID-19) pandemic, respiratory manifestations have been the mainstay of clinical diagnosis, laboratory evaluations, and ... ...

Abstract	Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant coronavirus disease 2019 (COVID-19) pandemic, respiratory manifestations have been the mainstay of clinical diagnosis, laboratory evaluations, and radiological investigations. As time passed, other pathological aspects of SARS-CoV-2 have been revealed. Various hemostatic abnormalities have been reported since the rise of the pandemic, which was sometimes superficial, transient, or fatal. Mild thrombocytopenia, thrombocytosis, venous, arterial thromboembolism, and disseminated intravascular coagulation are among the many hemostatic events associated with COVID-19. Venous thromboembolism necessitating therapeutic doses of anticoagulants is more frequently seen in severe cases of COVID-19, especially in patients admitted to intensive care units. Hemorrhagic complications rarely arise in COVID-19 patients either due to a hemostatic imbalance resulting from severe disease or as a complication of over anticoagulation. Although the pathogenesis of coagulation disturbance in SARS-CoV-2 infection is not yet understood, professional societies recommend prophylactic antithrombotic therapy in severe cases, especially in the presence of abnormal coagulation indices. The review article discusses the various available evidence on coagulation disorders, management strategies, outcomes, and prognosis associated with COVID-19 coagulopathy, which raises awareness about the importance of anticoagulation therapy for COVID-19 patients to guard against possible thromboembolic events.
Language	English
Publishing date	2022-09-20
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2222-0682
ISSN	2222-0682
DOI	10.5662/wjm.v12.i5.331
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Article ; Online: Reduced adhesive ligand density in engineered extracellular matrices induces an epithelial-mesenchymal-like transition.

Marlar, Saw / Abdellatef, Shimaa A / Nakanishi, Jun

Acta biomaterialia

2016 Volume 39, Page(s) 106–113

Abstract: Unlabelled: A synergistic effect of biochemical and mechanical cues emanating from the extracellular matrix (ECM) on inducing malignant transformation of epithelial cells has been observed recently. However, the effect of quantitative changes in ... ...

Abstract	Unlabelled: A synergistic effect of biochemical and mechanical cues emanating from the extracellular matrix (ECM) on inducing malignant transformation of epithelial cells has been observed recently. However, the effect of quantitative changes in biochemical stimuli on cell phenotype, without changes in ECM component and rigidity, remains unknown. To determine this effect, we grew Madin-Darby canine kidney epithelial cells (MDCK) on gold surfaces immobilized with varying densities of cyclic arginine-glycine-aspartate (cRGD) peptide and analyzed cell morphology, cell migration, cytoskeletal organization, and protein expression. Cells grown on a surface presenting a higher density of cRGD displayed an epithelial morphology and grew in clusters, while those grown on a diluted cRGD surface transformed into an elongated, fibroblast-like form with extensive scattering. Time-lapse imaging of cell clusters grown on the concentrated cRGD surface revealed collective migration with intact cell-cell contacts accompanied by the development of cortical actin. In contrast, cells migrated individually and formed stress fibers on the substrate with sparse cRGD. These data point towards transdifferentiation of epithelial cells to mesenchymal-like cells when plated on a diluted cRGD surface. Supporting this hypothesis, immunofluorescence microscopy and western blot analysis revealed increased membrane localization and total expression of N-cadherin and vimentin in cells undergoing mesenchymal-like transition. Taken together, these results suggest a possible role of decreased biochemical stimuli from the ECM in regulating epithelial phenotype switching. Statement of significance: Epithelial-mesenchymal transition (EMT) is a process where adherent epithelial cells convert into individual migratory mesenchymal phenotype. It plays an important role both in physiological and pathological processes. Recent studies demonstrate that the program is not only governed by soluble factors and gene expressions, but also modulated by biochemical and mechanical cues in ECMs. In this study, we developed chemically defined surfaces presenting controlled ECM ligand densities and studied their impact on the EMT progression. Morphological and biochemical analyses of epithelial cells cultured on the surfaces indicate the cells undergo an EMT-like transition on the diluted cRGD surface while retaining epithelial characteristics on the cRGD-rich substrate, suggesting an important role of the ECM ligand density in epithelial phenotype switching.
MeSH term(s)	Animals ; Cell Movement ; Cytoskeleton/metabolism ; Dogs ; Epithelial-Mesenchymal Transition ; Extracellular Matrix/chemistry ; Gold ; Ligands ; Madin Darby Canine Kidney Cells ; Peptides, Cyclic/chemistry ; Protein Biosynthesis ; Surface Properties ; Tissue Engineering
Chemical Substances	Ligands ; Peptides, Cyclic ; cyclic arginine-glycine-aspartic acid peptide ; Gold (7440-57-5)
Language	English
Publishing date	2016--15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2016.05.006
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