Directed vertical cell migration via bifunctionalized nanomaterials in 3D step-gradient nanocomposite hydrogels

2020 ◽  
Vol 8 (20) ◽  
pp. 5628-5637
Author(s):  
Andisheh Motealleh ◽  
Nermin S. Kehr

Step-gradient scaffolds promote healthy cell migration, while inhibit the migration of cancerous cells in the XZ plane of the 2GradNS.

2019 ◽  
Author(s):  
Jingjing Li ◽  
Andrew D. Economou ◽  
Jeremy B.A. Green

AbstractEpithelial bending is a fundamental process that shapes organs during development. All currently known mechanisms involve cells locally changing shape from columnar to wedge-shaped. Often this shape change occurs by cytoskeletal contraction at cell apices (“apical constriction”) but mechanisms such as basal nuclear positioning (“basal wedging”) or extrinsic compression are also known. Here we demonstrate a completely different mechanism which occurs without cell wedging. In mammalian salivary glands and teeth, we show that initial invagination occurs through coordinated vertical cell movement. Specifically, we show that cells towards the periphery of the placode move vertically upwards while their more central neighbours move downwards to create the invagination. We further show that this occurs by active cell-on-cell migration: outer cells migrate with an apical leading edge protrusion, depressing the central cells to “telescope” the epithelium downwards into the underlaying mesenchyme. Cells remain basally attached to the underlying lamina while their apical protrusions are dynamic and planar polarised centripetally. These protrusions depend on the actin cytoskeleton, and inhibition of the branching molecule Arp2/3 inhibits them and the invagination. FGF and Hedgehog morphogen signals are also required, with FGF providing a directional cue. These findings show that epithelial bending can be achieved by novel morphogenetic mechanism of coordinated cell rearrangement quite distinct from previously recognised invagination processes.


2019 ◽  
Author(s):  
T. Yaginuma ◽  
K. Kushiro ◽  
M. Takai

AbstractIn recent years, many types of micro-engineered platform have been fabricated to investigate the influences of surrounding microenvironments on cell migration. Previous researches demonstrate that microgroove-based topographies can influence cell motilities of normal and cancerous cells differently. In this paper, the microgroove wall angle is altered from obtuse to acute angles and the resulting differences in the responses of normal and cancer cells are investigated to explore the geometrical characteristics that can efficiently distinguish normal and cancer cells. Interestingly, trends in cell motilities of normal and cancer cells as the wall angles are varied between 60-120° were different, and in particular, invasive cancer cells exhibit a unique, oscillatory migratory behavior. Results from the immunostaining of cell mechanotransduction components suggest that this difference stems from directional extension and adhesion behaviors of each cell type. In addition, the specific behaviors of invasive cancer cells are found to be dependent on the myosin II activity, and modulating the activity can revert cancerous behaviors to normal ones. These novel findings on the interactions of acute angle walls and cancer cell migration provide a new perspective on cancer metastasis and additional strategies via microstructure geometries for the manipulations of cell behaviors in microscale biodevices.Statement of SignificanceCancer metastasis is the leading cause of cancer patient deaths, and yet how the microstructures within the body affect this cell migration phenomenon is not well understood. In this paper, microdevices containing microgroove structures of varying geometries, in particular obtuse and acute angles, were utilized to monitor cell motilities of various cancer cells to understand the influences of the geometrical features of microstructures on cancer metastasis. Surprisingly, it was found that the acute angle geometries lowered the persistence of migration for cancer cells, which was a totally different response from non-cancerous cells. These new findings would enable the next-generation biodevices to analyze, separate and capture cancer cells, as well as shed light onto the underlying mechanisms of cancer metastasis.


2020 ◽  
Vol 14 (1) ◽  
pp. 79-87
Author(s):  
Seyed H. Shahcheraghi ◽  
Marzieh Lotfi ◽  
Mohammad Soukhtanloo ◽  
Majid Ghayour Mobarhan ◽  
Hossein Z. Jaliani ◽  
...  

Background: Glioblastoma is one of the most aggressive tumors of central nervous system. Galbanic acid, a natural sesquiterpene coumarin, has shown favorable effects on cancerous cells in previous studies. Objective: The aim of the present work was to evaluate the effects of galbanic acid on proliferation, migration, and apoptosis of the human malignant glioblastoma (U87) cells. Methods: Anti-proliferative activity of the compound was determined by MTT assay. Cell cycle alterations and apoptosis were analyzed via flow cytometry. Action on cell migration was evaluated by scratch assay and gelatin zymography. Quantitative Real-Time PCR was used to determine the expression of genes involved in cell migration (matrix metalloproteinases, MMPs) and survival (the pathways of PI3K/Akt/mTOR and WNT/β-catenin). Alteration in the level of protein Akt was determined by Western blotting. Results: Galbanic acid significantly decreased cell proliferation, inhibited cell cycle, and stimulated apoptosis of the glioblastoma cells. Also, it could decrease migration capability of glioblastoma cells, which was accompanied by an inhibition in the activity and expression of MMP2 and MMP9. While galbanic acid reduced the gene expression of Akt, mTOR, and PI3K and increased the PTEN expression, it had no significant effect on WNT, β-catenin, and APC genes. Also, the protein level of p-Akt decreased after treatment with galbanic acid. The effects of galbanic acid were observed at concentrations lower than those of temozolomide. Conclusion: Galbanic acid decreased proliferation, cell cycle progression, and survival of glioblastoma cells through inhibiting PI3K/Akt/mTOR pathway. This compound also reduced migration capability of the cells by suppressing the activity and expression of MMPs.


2019 ◽  
Vol 11 (4) ◽  
pp. 045015 ◽  
Author(s):  
Andisheh Motealleh ◽  
Betül Çelebi-Saltik ◽  
Nihal Ermis ◽  
Sacha Nowak ◽  
Ali Khademhosseini ◽  
...  

Author(s):  
J. Roemer ◽  
S.R. Simon

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.


2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.


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