scholarly journals Single Cell Mechanotype and Associated Molecular Changes in Urothelial Cell Transformation and Progression

Author(s):  
Weibo Yu ◽  
Qing-Yi Lu ◽  
Shivani Sharma ◽  
Chau Ly ◽  
Dino Di Carlo ◽  
...  

Cancer cell mechanotype changes are newly recognized cancer phenotypic events, whereas metastatic cancer cells show decreased cell stiffness and increased deformability relative to normal cells. To further examine how cell mechanotype changes in early stages of cancer transformation and progression, an in vitro multi-step human urothelial cell carcinogenic model was used to measure cellular Young’s modulus, deformability, and transit time using single-cell atomic force microscopy, microfluidic-based deformability cytometry, and quantitative deformability cytometry, respectively. Measurable cell mechanotype changes of stiffness, deformability, and cell transit time occur early in the transformation process. As cells progress from normal, to preinvasive, to invasive cells, Young’s modulus of stiffness decreases and deformability increases gradually. These changes were confirmed in three-dimensional cultured microtumor masses and urine exfoliated cells directly from patients. Using gene screening and proteomics approaches, we found that the main molecular pathway implicated in cell mechanotype changes appears to be epithelial to mesenchymal transition.

2019 ◽  
Vol 20 (18) ◽  
pp. 4351
Author(s):  
Renata Szydlak ◽  
Marcin Majka ◽  
Małgorzata Lekka ◽  
Marta Kot ◽  
Piotr Laidler

Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are multipotent stem cells that can be used in regenerative medicine. However, to reach the high therapeutic efficacy of WJ-MSCs, it is necessary to obtain a large amount of MSCs, which requires their extensive in vitro culturing. Numerous studies have shown that in vitro expansion of MSCs can lead to changes in cell behavior; cells lose their ability to proliferate, differentiate and migrate. One of the important measures of cells’ migration potential is their elasticity, determined by atomic force microscopy (AFM) and quantified by Young’s modulus. This work describes the elasticity of WJ-MSCs during in vitro cultivation. To identify the properties that enable transmigration, the deformability of WJ-MSCs that were able to migrate across the endothelial monolayer or Matrigel was analyzed by AFM. We showed that WJ-MSCs displayed differences in deformability during in vitro cultivation. This phenomenon seems to be strongly correlated with the organization of F-actin and reflects the changes characteristic for stem cell maturation. Furthermore, the results confirm the relationship between the deformability of WJ-MSCs and their migration potential and suggest the use of Young’s modulus as one of the measures of competency of MSCs with respect to their possible use in therapy.


Materials ◽  
2020 ◽  
Vol 13 (22) ◽  
pp. 5130
Author(s):  
Renhao Xue ◽  
Dong Wang ◽  
Dawei Yang ◽  
Ligang Zhang ◽  
Xiaoning Xu ◽  
...  

The microstructure, mechanical properties, magnetic susceptibility, electrochemical corrosion performance, in vitro cell compatibility and blood consistency of Zr-16Nb-xTi (x = 0, 4, 8, 12 and 16 wt.%) materials were investigated as potential materials for biomedical implants. X-ray diffraction (XRD) and Transmission electron microscopy (TEM) analyses revealed the secondary phase martensite α’ formed during the quenching process. The phase composition contained metastable β and martensite α’, resulting from Ti addition. These phase constitutions were the main causes of a low Young’s modulus and magnetic susceptibility. The in vitro cytocompatibility analysis illustrated that the MG63 cells maintained high activity (from 91% to 97%) after culturing in Zr-16Nb-xTi extraction media for 12 days due to the high internal biocompatibility of Zr, Nb and Ti elements, as well as the optimal corrosion resistance of Zr-16Nb-xTi. On the basis of Inductively coupled plasma optical emission spectrometry (ICP-OES) ion release studies, the concentration of Zr, Nb and Ti was noted to reach the equipment detective limit of 0.001 mg/L, which was much lower than pure Ti. With respect to the corrosion behavior in Hank’s solution, Zr-16Nb-16Ti displayed superior properties, possessing the lowest corrosion current density and widest passivation region, attributed to the addition of Ti. The blood compatibility test illustrated that the Zr-16Nb-xTi materials were nonhemolytic, and the platelets maintained a spherical shape, with no aggregation or activation on Zr-16Nb-xTi. Overall, Ti addition has obvious effects on the developed Zr-16Nb-xTi alloys, and Zr-16Nb-4Ti exhibited low magnetic susceptibility, low modulus, good biocompatibility and proper corrosion properties, demonstrating the potential of use as implant biomaterials.


2020 ◽  
Vol 12 (5) ◽  
pp. 1880 ◽  
Author(s):  
Ahmed Abdulhamid Mahmoud ◽  
Salaheldin Elkatatny ◽  
Dhafer Al Shehri

Prediction of the mechanical characteristics of the reservoir formations, such as static Young’s modulus (Estatic), is very important for the evaluation of the wellbore stability and development of the earth geomechanical model. Estatic considerably varies with the change in the lithology. Therefore, a robust model for Estatic prediction is needed. In this study, the predictability of Estatic for sandstone formation using four machine learning models was evaluated. The design parameters of the machine learning models were optimized to improve their predictability. The machine learning models were trained to estimate Estatic based on bulk formation density, compressional transit time, and shear transit time. The machine learning models were trained and tested using 592 well log data points and their corresponding core-derived Estatic values collected from one sandstone formation in well-A and then validated on 38 data points collected from a sandstone formation in well-B. Among the machine learning models developed in this work, Mamdani fuzzy interference system was the highly accurate model to predict Estatic for the validation data with an average absolute percentage error of only 1.56% and R of 0.999. The developed static Young’s modulus prediction models could help the new generation to characterize the formation rock with less cost and safe operation.


2006 ◽  
Vol 975 ◽  
Author(s):  
Andrei Stanishevsky ◽  
Shafiul Chowdhury ◽  
Nathaniel Greenstein ◽  
Helene Yockell-Lelievre ◽  
Jari Koskinen

ABSTRACTThe hydroxyapatite (HA) based bioceramic materials are usually prepared at high sintering temperatures to attain suitable mechanical properties. The sintering process usually results in a material which is compositionally and morphologically different from nonstoichiometric nano-crystalline HA phase of hard tissue. At the same time, HA particulates used as precursors in ceramic manufacturing are often very similar to the natural HA nanocrystals. It has been shown that synthetic nanoparticle HA (nanoHA) based materials improve the biological response in vitro and in vivo, but the information on mechanical properties of these materials is scarce.In this work we studied the HA nanoparticle (10 – 80 nm mean size) coatings with 30 – 70% porosity prepared by a dip-coating technique on Ti and TiN substrates. It has been found that the mechanical properties of HA nanoparticle coatings are strongly influenced by the initial size, morphology, and surface treatment of nanoparticles. The nanoindentation Young's modulus and hardness of as–deposited nanoHA coatings were in the range of 2.5 – 6.9 GPa and 80 – 230 MPa, respectively. The coatings were stable after annealing up to at least 600 °C, reaching the Young's modulus up to 23 GPa and hardness up to 540 MPa, as well as in simulated body fluids.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Loukia G. Karacosta ◽  
Benedict Anchang ◽  
Nikolaos Ignatiadis ◽  
Samuel C. Kimmey ◽  
Jalen A. Benson ◽  
...  

AbstractElucidating the spectrum of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in clinical samples promises insights on cancer progression and drug resistance. Using mass cytometry time-course analysis, we resolve lung cancer EMT states through TGFβ-treatment and identify, through TGFβ-withdrawal, a distinct MET state. We demonstrate significant differences between EMT and MET trajectories using a computational tool (TRACER) for reconstructing trajectories between cell states. In addition, we construct a lung cancer reference map of EMT and MET states referred to as the EMT-MET PHENOtypic STAte MaP (PHENOSTAMP). Using a neural net algorithm, we project clinical samples onto the EMT-MET PHENOSTAMP to characterize their phenotypic profile with single-cell resolution in terms of our in vitro EMT-MET analysis. In summary, we provide a framework to phenotypically characterize clinical samples in the context of in vitro EMT-MET findings which could help assess clinical relevance of EMT in cancer in future studies.


2019 ◽  
Vol 141 (8) ◽  
Author(s):  
Shan Sun ◽  
Djanybek Adyshev ◽  
Steven Dudek ◽  
Amit Paul ◽  
Andrew McColloch ◽  
...  

Cell mechanics has been shown to regulate stem cell differentiation. We have previously reported that altered cell stiffness of mesenchymal stem cells can delay or facilitate biochemically directed differentiation. One of the factors that can affect the cell stiffness is cholesterol. However, the effect of cholesterol on differentiation of human mesenchymal stem cells remains elusive. In this paper, we demonstrate that cholesterol is involved in the modulation of the cell stiffness and subsequent adipogenic differentiation. Rapid cytoskeletal actin reorganization was evident and correlated with the cell's Young's modulus measured using atomic force microscopy. In addition, the level of membrane-bound cholesterol was found to increase during adipogenic differentiation and inversely varied with the cell stiffness. Furthermore, cholesterol played a key role in the regulation of the cell morphology and biomechanics, suggesting its crucial involvement in mechanotransduction. To better understand the underlying mechanisms, we investigated the effect of cholesterol on the membrane–cytoskeleton linker proteins (ezrin and moesin). Cholesterol depletion was found to upregulate the ezrin expression which promoted cell spreading, increased Young's modulus, and hindered adipogenesis. In contrast, cholesterol enrichment increased the moesin expression, decreased Young's modulus, and induced cell rounding and facilitated adipogenesis. Taken together, cholesterol appears to regulate the stem cell mechanics and adipogenesis through the membrane-associated linker proteins.


RSC Advances ◽  
2020 ◽  
Vol 10 (40) ◽  
pp. 23582-23591
Author(s):  
Xin Liu ◽  
Yumei Niu ◽  
Weili Xie ◽  
Daqing Wei ◽  
Qing Du

To avoid the failure of clinical surgery due to “stress shielding” and the loosening of an implant, a new type of alloy, Ti–24Nb–4Zr–8Sn (TNZS), with a low Young's modulus acted as a new implant material in this work.


2012 ◽  
Vol 27 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Michela Gioffrè ◽  
Paola Torricelli ◽  
Silvia Panzavolta ◽  
Katia Rubini ◽  
Adriana Bigi

The effect of the film-forming solution pH on the triple-helix content, thermal stability, and mechanical properties of gelatin films was investigated. The films were prepared from solutions at different pHs of type A pigskin gelatin, and their mechanical characteristics were determined. At pHs higher than 9 and lower than 5, Young’s modulus, E, and the stress at break, σb, of the films decreased significantly. Cross-linking with genipin reduced deformation at break, ϵb, and increased Young’s modulus. The intensity of the 1.1-nm X-ray diffraction reflection and the denaturation enthalpy decreased at these pHs, indicating that the triple helix reduced. Preliminary in vitro tests on the cross-linked samples indicated good cell proliferation and viability.


2012 ◽  
Vol 17 (4) ◽  
pp. 048002 ◽  
Author(s):  
Rolando J. González-Peña ◽  
Rosario Salvador ◽  
Rosa M. Cibrián ◽  
René A. Martinez-Celorio ◽  
Francisco J. López ◽  
...  

2021 ◽  
Vol 18 (9) ◽  
pp. 1791-1798
Author(s):  
Ola Tarawneh ◽  
Ameen Rasheed Al-Ass ◽  
Rania Hamed ◽  
Suhair Sunoqrot ◽  
Lina Hasan ◽  
...  

Purpose: To prepare emulsion-based Intrapocket polymeric films for the treatment of periodontitis. Method: Films were fabricated by dehydration of an emulsion containing k-carrageenan (KC) in aqueous phase and Compritol® 888 ATO (Compritol® ) or Dimodan® UJ (DU® ) or different ratios of both. The resulting films were characterized by mechanical texture analyser to determine Young’s modulus and tensile strength. Glass transition temperature (Tg) of the films was evaluated by dynamic mechanical and thermal analyser while surface morphology was evaluated using scanning electron microscope. In-vitro drug release was conducted in pre-warmed phosphate buffer. Bacterial adherence was assessed after 24 h. Results: Young’s modulus was highest for KC films to which no lipid was added (5.33 ± 0.38 GPa) and decreased following lipid incorporation. Tg was highest in KC films (106.25 ± 4.53 ° C) but decreased upon addition of lipids. The surface of KC was smooth but roughness increased with increasing Compritol® load. Drug release from KC films was complete (99.80 ± 8.43 %) after 2 h; however, upon adding lipid, the release was extended 8 h and was affected by lipid type and ratio. Microbiologic assay demonstrated noticeable reduction in viable count compared to control and was affected by lipid type and ratio. The film formulated from a combination of DU® and Compritol® in a ratio of 80:20 was strong, flexible and reduced microbial adherence. Moreover, it showed a smooth surface and extended release for over 8 h. Conclusion: Intra-pocket films were prepared by drying emulsion-based films. Resulted films were strong, flexible, prolonged drug release over 8 h and could lower bacterial growth. The prepared film may offer efficient treatment in periodontitis patients.


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