Shimaa Abdelazim Abdellatef Abdelaleem
@nims.go.jp
Mechanobiology group
National Institute for Material Science
EDUCATION
PhD Waseda University
RESEARCH, TEACHING, or OTHER INTERESTS
Multidisciplinary, Cell Biology, Biomaterials
Scopus Publications
Scopus Publications
Aiwen Zhang, Shimaa A. Abdellatef, and Jun Nakanishi
Springer Science and Business Media LLC
Hongxin Wang, Han Zhang, Ryo Tamura, Bo Da, Shimaa A. Abdellatef, Ikumu Watanabe, Nobuyuki Ishida, Daisuke Fujita, Nobutaka Hanagata, Tomoki Nakagawa,et al.
Informa UK Limited
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.
Shinya Sakakibara, Shimaa A. Abdellatef, Shota Yamamoto, Masao Kamimura, and Jun Nakanishi
Informa UK Limited
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.
Shimaa A Abdellatef, Hisashi Tadakuma, Kangmin Yan, Takashi Fujiwara, Kodai Fukumoto, Yuichi Kondo, Hiroko Takazaki, Rofia Boudria, Takuo Yasunaga, Hideo Higuchi,et al.
eLife Sciences Publications, Ltd
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.
Alice Chinghsuan Chang, Koichiro Uto, Shimaa A. Abdellatef, and Jun Nakanishi
American Chemical Society (ACS)
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.
Shimaa A. Abdellatef and Jun Nakanishi
Elsevier BV
Saw Marlar, Shimaa A. Abdellatef, and Jun Nakanishi
Elsevier BV
Yoshihisa Shimizu, Masao Kamimura, Shota Yamamoto, Shimaa A. Abdellatef, Kazuo Yamaguchi, and Jun Nakanishi
Springer Science and Business Media LLC
This paper describes a facile method for the preparation of photoactivatable substrates with tuned surface density of an extracellular matrix peptide to resolve the impacts of biochemical and mechanical cues on collective cell migration. The controllability of surface ligand density was validated by cell adhesion and migration tests, complemented with fluorescence observation of an alternative ligand. Depending on the surface ligand density, HeLa cells either kept or lost collective characteristics. The present materials will be useful to address mechanobiology of collective cell migration.
Shimaa A. Abdellatef, Riho Tange, Takeshi Sato, Akihiko Ohi, Toshihide Nabatame, and Akiyoshi Taniguchi
Hindawi Limited
In drug discovery programs, the alteration betweenin vivoandin vitrocellular responses to drug represents one of the main challenges. Since the variation in the native extracellular matrix (ECM) betweenin vivoand 2Din vitroconditions is one of the key reasons for such discrepancies, thus the utilization of substrate that likely mimics ECM characteristics (topography, stiffness, and chemical composition) is needed to overcome such problem. Here, we investigated the role of substrate nanotopography as one of the major determinants of hepatic cellular responses to a chemotherapeutic agent “cisplatin.” We studied the substratum induced variations in cisplatin cytotoxicity; a higher cytotoxic response to cisplatin was observed for cells cultured on the nanopattern relative to a flat substrate. Moreover, the nanofeatures with grating shapes that mimic the topography of major ECM protein constituents (collagen) induced alterations in the cellular orientation and chromatin condensation compared to flat surfaces. Accordingly, the developments of biomimetic substrates with a particular topography could have potentials in drug development analyses to reflect more physiological mimicry conditionsin vitro.
Shimaa Abdellatef, Akihiko Ohi, Toshihide Nabatame, and Akiyoshi Taniguchi
MDPI AG
Physical topographical features and/or chemical stimuli to the extracellular matrix (ECM) provide essential cues that manipulate cell functions. From the physical point of view, contoured nanostructures are very important for cell behavior in general, and for cellular functions. From the chemical point of view, ECM proteins containing an RGD sequence are known to alter cell functions. In this study, the influence of integrated physical and chemical cues on a liver cell line (HepG2) was investigated. To mimic the physical cues provided by the ECM, amorphous TiO2 nanogratings with specific dimensional and geometrical characteristics (nanogratings 90 nm wide and 150 nm apart) were fabricated. To mimic the chemical cues provided by the ECM, the TiO2 inorganic film was modified by immobilization of the RGD motif. The hepatic cell line morphological and functional changes induced by simultaneously combining these diversified cues were investigated, including cellular alignment and the expression of different functional proteins. The combination of nanopatterns and surface modification with RGD induced cellular alignment and expression of functional proteins, indicating that physical and chemical cues are important factors for optimizing hepatocyte function.
Shimaa A. Abdellatef, Akihiko Ohi, Toshihide Nabatame, and Akiyoshi Taniguchi
Royal Society of Chemistry (RSC)
To investigate the influence of bio-inspired metallic superficial topography on the cellular behaviour of a hepatocyte cell line, TiO2 nanopatterns with diversified shapes and heterotropic lateral dimensions were fabricated using electron beam lithography and atomic layer deposition. The dimensional uniformity and shape diversity of the nanopatterns were confirmed using scanning electron microscopy and atomic force microscopy. These topographical nanocues provide good tools for controlling and regulating multiple hepatocellular functions. The expressions of functional proteins such as albumin, transferrin and cytochrome P450 were tested as functional markers. In addition, the change in cellular orientation, cell alignment and native extracellular matrix (ECM) assembly induced by these well-defined nanotopographies were observed. Twelve hours after cell seeding, TiO2 nanogratings with a lateral dimension of 240 nm showed a higher degree of functional protein expression compared to other nanotopographical substrates and a flat surface. These findings suggest that the TiO2 surface resembles a hierarchically-extended collagen nanofibrillar surface and could be recognized by hepatocytes, allowing the proper cytoskeletal orientation and cellular integrity. This TiO2 nanopattern with a specific shape and dimension (240 nm) might therefore emulate ECM biophysical cues, and the intrinsic topography of TiO2 surfaces might evoke enhanced cellular responses. These unique surfaces could be further exploited for tissue engineering and bioreactor technology.
S. A. El‐Safty, S. Abdellatef, M. Ismael, and A. Shahat
Wiley
AbstractBecause toxic heavy metals tend to bioaccumulate, they represent a substantial human health hazard. Various methods are used to identify and quantify toxic metals in biological tissues and environment fluids, but a simple, rapid, and inexpensive system has yet to be developed. To reduce the necessity for instrument‐dependent analysis, we developed a single, pH‐dependent, nanosphere (NS) sensor for naked‐eye detection and removal of toxic metal ions from drinking water and physiological systems (i.e., blood). The design platform for the optical NS sensor is composed of double mesoporous core–shell silica NSs fabricated by one‐pot, template‐guided synthesis with anionic surfactant. The dense shell‐by‐shell NS construction generated a unique hierarchical NS sensor with a hollow cage interior to enable accessibility for continuous monitoring of several different toxic metal ions and efficient multi‐ion sensing and removal capabilities with respect to reversibility, longevity, selectivity, and signal stability. Here, we examined the application of the NS sensor for the removal of toxic metals (e.g., lead ions from a physiological system, such as human blood). The findings show that this sensor design has potential for the rapid screening of blood lead levels so that the effects of lead toxicity can be avoided.