scholarly journals An in-silico Investigation Into the Role of Strain and Structure on Vascular Smooth Muscle Cell Growth

2021 ◽  
Vol 9 ◽  
Author(s):  
Orla M. McGee ◽  
David R. Nolan ◽  
Pattie S. Mathieu ◽  
Caitríona Lally
Keyword(s):  
Smooth Muscle ◽  
Cell Growth ◽  
In Silico ◽  
Cellular Response ◽  
Soft Tissues ◽  
Cyclic Strain ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Collective Response ◽  
In Cells

The orientation of vascular cells can greatly influence the in vivo mechanical properties and functionality of soft vascular tissues. How cell orientation mediates the growth response of cells is of critical importance in understanding the response of soft tissues to mechanical stimuli or injury. To date, considerable evidence has shown that cells align with structural cues such as collagen fibers. However, in the presence of uniaxial cyclic strain on unstructured substrates, cells generally align themselves perpendicularly to the mechanical stimulus, such as strain, a phenomenon known as “strain avoidance.” The cellular response to this interplay between structural cues and a mechanical stimulus is poorly understood. A recent in vitro experimental study in our lab has investigated both the individual and collective response of rat aortic smooth muscle cells (RASMC) to structural (collagenous aligned constructs) and mechanical (cyclic strain) cues. In this study, a 2D agent-based model (ABM) is developed to simulate the collective response of RASMC to varying amplitudes of cyclic strain (0–10%, 2–8%, 4–6%) when seeded on unstructured (PDMS) and structured (decellularized collagenous tissue) constructs. An ABM is presented that is fit to the experimental outcomes in terms of cellular alignment and cell growth on PDMS substrates, under cyclic strain amplitudes of (4–6%, 2–8%, 0–10%) at 24 and 72 h timepoints. Furthermore, the ABM can predict RASMC alignment and change in cell number on a structured construct at a cyclic strain amplitude of 0–10% after 10 days. The ABM suggests that strain avoidance behavior observed in cells is dominated by selective cell proliferation and apoptosis at these early time points, as opposed to cell re-orientation, i.e., cells perpendicular to the strain increase their rate of proliferation, whilst the rate of apoptosis simultaneously increases in cells parallel to the strain direction. The development of in-silico modeling platforms, such as that presented here, allow for further understanding of the response of cells to changes in their mechanical environment. Such models offer an efficient and robust means to design and optimize the compliance and topological structure of implantable devices and could be used to aid the design of next-generation vascular grafts and stents.

scholarly journals Manganese Suppresses the Haploinsufficiency of Heterozygous trpy1Δ/TRPY1 Saccharomyces cerevisiae Cells and Stimulates the TRPY1-Dependent Release of Vacuolar Ca2+ under H2O2 Stress

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 79 ◽  
Author(s):  
Lavinia Ruta ◽  
Ioana Nicolau ◽  
Claudia Popa ◽  
Ileana Farcasanu
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Cellular Response ◽  
Trp Channels ◽  
Homozygous Deletion ◽  
Growth Defect ◽  
Mechanical Stimuli ◽  
Hyperosmotic Shock ◽  
Diploid Cells ◽  
In Cells

Transient potential receptor (TRP) channels are conserved cation channels found in most eukaryotes, known to sense a variety of chemical, thermal or mechanical stimuli. The Saccharomyces cerevisiae TRPY1 is a TRP channel with vacuolar localization involved in the cellular response to hyperosmotic shock and oxidative stress. In this study, we found that S. cerevisiae diploid cells with heterozygous deletion in TRPY1 gene are haploinsufficient when grown in synthetic media deficient in essential metal ions and that this growth defect is alleviated by non-toxic Mn2+ surplus. Using cells expressing the Ca2+-sensitive photoprotein aequorin we found that Mn2+ augmented the Ca2+ flux into the cytosol under oxidative stress, but not under hyperosmotic shock, a trait that was absent in the diploid cells with homozygous deletion of TRPY1 gene. TRPY1 activation under oxidative stress was diminished in cells devoid of Smf1 (the Mn2+-high-affinity plasma membrane transporter) but it was clearly augmented in cells lacking Pmr1 (the endoplasmic reticulum (ER)/Golgi located ATPase responsible for Mn2+ detoxification via excretory pathway). Taken together, these observations lead to the conclusion that increased levels of intracytosolic Mn2+ activate TRPY1 in the response to oxidative stress.

INK-JET PRINTED STRETCHABLE SENSORS FOR CELL MONITORING UNDER MECHANICAL STIMULI: A FEASIBILITY STUDY

2019 ◽  
Vol 19 (06) ◽  
pp. 1950049 ◽  
Author(s):  
SARAH TONELLO ◽  
MICHELA BORGHETTI ◽  
NICOLA F. LOPOMO ◽  
MAURO SERPELLONI ◽  
EMILIO SARDINI ◽  
...  
Keyword(s):  
Cyclic Strain ◽  
Mechanical Stimulus ◽  
Research Field ◽  
Stretchable Electronics ◽  
Present System ◽  
Mechanical Stimuli ◽  
Ink Jet ◽  
Cell Monitoring ◽  
Cell Concentrations ◽  
Stretchable Sensors

Impedance-based sensors represent a promising tool for cell monitoring to improve current invasive biological assays. A novel research field is represented by measurements performed in dynamic conditions, monitoring cells (e.g., myocytes) for which the mechanical stimulus plays an important role for promoting maturation. In this picture, we applied printed and stretchable electronics principles, developing a system able to evaluate cells adhesion during substrate cyclic strain. Cytocompatible and stretchable sensors were ink-jet printed using carbon-based ink on crosslinked poly([Formula: see text]-caprolactone) electrospun mats. Moreover, a customized stretching device was produced, with a complete user interface to control testing condition, validated in order to correlate impedance changes with myoblasts — i.e., myocytes precursors — adhesion. Overall system sensitivity was evaluated using three different cell concentrations and DAPI imaging assay was performed to confirm myoblast adhesion. Preliminary results showed the possibility to correlate an average increase of impedance magnitude of 1[Formula: see text]k[Formula: see text] every 15,000 cells/cm2 seeded, suggesting the possibility to discriminate between different cell concentrations, with a sensitivity of 80[Formula: see text]m[Formula: see text]/(cells/cm2). In conclusion, the present system might be generalized in the development of future applications, including the differentiation process of cardiac myocytes with the aid of mechanical stimuli.

scholarly journals Effects of Length and Location on the Cellular Response to Double-Stranded RNA

2004 ◽  
Vol 68 (3) ◽  
pp. 432-452 ◽  
Author(s):  
Qiaoqiao Wang ◽  
Gordon G. Carmichael
Keyword(s):  
Cell Growth ◽  
Viral Infection ◽  
Normal Cell ◽  
Cellular Response ◽  
Viral Infections ◽  
Cellular Responses ◽  
Double Stranded Rna ◽  
Antiviral Responses ◽  
And Function ◽  
In Cells

SUMMARY Since double-stranded RNA (dsRNA) has not until recently generally been thought to be deliberately expressed in cells, it has commonly been assumed that the major source of cellular dsRNA is viral infections. In this view, the cellular responses to dsRNA would be natural and perhaps ancient antiviral responses. While the cell may certainly react to some dsRNAs as an antiviral response, this does not represent the only response or even, perhaps, the major one. A number of recent observations have pointed to the possibility that dsRNA molecules are not seen only as evidence of viral infection or recognized for degradation because they cannot be translated. In some instances they may also play important roles in normal cell growth and function. The purpose of this review is to outline our current understanding of the fate of dsRNA in cells, with a focus on the apparent fact that their fates and functions appear to depend critically not only on where in the cell dsRNA molecules are found, but also on how long they are and perhaps on how abundant they are.

Cellular Response to Stretch by Modulation of Cytoskeletal Tension in Two Distinct Phases

2011 ◽  
Author(s):  
Jennifer Mann ◽  
Raymond Lam ◽  
Jianping Fu
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cellular Response ◽  
Cell Structure ◽  
Muscle Cells ◽  
Underlying Mechanism ◽  
Dynamic Responses ◽  
Mechanistic Study ◽  
Mechanical Stimuli ◽  
External Forces

External forces are increasingly recognized as major regulators of cell structure and function, yet the underlying mechanism by which cells sense force and transduce it into intracellular biochemical signals and behavioral responses (‘mechanotransduction’) is largely undetermined. To aid in the mechanistic study of mechanotransduction, we devised a novel cell stretching device that allows for quantitative control and real-time measurement of mechanical stimuli and cellular biomechanical responses. Using this device, we studied the subcellular dynamic responses of contractile force and adhesion remodeling of vascular smooth muscle cells (VSMCs) to stretch. Our data showed that VSMCs could acutely enhance their contraction to resist rapid cell deformation, but they could also allow slow adaptive inelastic cytoskeletal reorganization in response to sustained cell stretch. Our study may help elucidate the mechanotransduction system in smooth muscle cells, and thus contribute to our understanding of pressure-induced vascular disease processes.

scholarly journals Evaluation of fundamental hypotheses underlying constrained mixture models of arterial growth and remodelling

2009 ◽  
Vol 367 (1902) ◽  
pp. 3585-3606 ◽  
Author(s):  
A. Valentín ◽  
J. D. Humphrey
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mixture Models ◽  
Soft Tissues ◽  
Mass Density ◽  
Constitutive Relations ◽  
Muscle Cells ◽  
Combined Effects ◽  
Mechanical Stimuli ◽  
Constrained Mixture

Evolving constituent composition and organization are important determinants of the biomechanical behaviour of soft tissues. In arteries, vascular smooth muscle cells and fibroblasts continually produce and degrade matrix constituents in preferred modes and at altered rates in response to changing mechanical stimuli. Smooth muscle cells similarly exhibit vasoactive changes that contribute to the control of overall structure, function and mechanical behaviour. Constrained mixture models provide a useful framework in which to quantify arterial growth and remodelling for they can account for cell-mediated changes in individual structurally significant constituents. Our simulations show that the combined effects of changing mass density turnover and vasoactivity, as well as the prestretch at which constituents are incorporated within extant matrix, are essential to capture salient features of bounded arterial growth and remodelling. These findings emphasize the importance of formulating biologically motivated constitutive relations in any theory of growth and remodelling and distinct advantages of the constrained mixture approach, in particular.

scholarly journals Initial mechanical conditions within an optimized bone scaffold do not ensure bone regeneration – an in silico analysis

2021 ◽  
Author(s):  
Camille Perier-Metz ◽  
Georg N. Duda ◽  
Sara Checa
Keyword(s):  
Bone Regeneration ◽  
In Silico ◽  
Volume Fraction ◽  
Computer Modelling ◽  
Mechanical Strain ◽  
In Silico Analysis ◽  
Bone Volume ◽  
Mechanical Stimuli ◽  
Design Strategies ◽  
Scaffold Design

AbstractLarge bone defects remain a clinical challenge because they do not heal spontaneously. 3-D printed scaffolds are a promising treatment option for such critical defects. Recent scaffold design strategies have made use of computer modelling techniques to optimize scaffold design. In particular, scaffold geometries have been optimized to avoid mechanical failure and recently also to provide a distinct mechanical stimulation to cells within the scaffold pores. This way, mechanical strain levels are optimized to favour the bone tissue formation. However, bone regeneration is a highly dynamic process where the mechanical conditions immediately after surgery might not ensure optimal regeneration throughout healing. Here, we investigated in silico whether scaffolds presenting optimal mechanical conditions for bone regeneration immediately after surgery also present an optimal design for the full regeneration process. A computer framework, combining an automatic parametric scaffold design generation with a mechano-biological bone regeneration model, was developed to predict the level of regenerated bone volume for a large range of scaffold designs and to compare it with the scaffold pore volume fraction under favourable mechanical stimuli immediately after surgery. We found that many scaffold designs could be considered as highly beneficial for bone healing immediately after surgery; however, most of them did not show optimal bone formation in later regenerative phases. This study allowed to gain a more thorough understanding of the effect of scaffold geometry changes on bone regeneration and how to maximize regenerated bone volume in the long term.

scholarly journals Assessment and Imaging of Intracellular Magnesium in SaOS-2 Osteosarcoma Cells and Its Role in Proliferation

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1376
Author(s):  
Concettina Cappadone ◽  
Emil Malucelli ◽  
Maddalena Zini ◽  
Giovanna Farruggia ◽  
Giovanna Picone ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Magnesium Deficiency ◽  
Acid Synthesis ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
High Concentration ◽  
Proliferating Cells ◽  
Intracellular Magnesium ◽  
In Cells

Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2–3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth.

STRETCHABLE Lab-on-Chip Device With Impedance Spectroscopy Capability for Mammalian Cell Studies

2016 ◽  
Author(s):  
Xudong Zhang ◽  
Anis Nurashikin Nordin ◽  
Fang Li ◽  
Ioana Voiculescu
Keyword(s):  
Impedance Spectroscopy ◽  
Mammalian Cells ◽  
Dynamic Environment ◽  
Cyclic Strain ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Aortic Endothelial Cells ◽  
Lab On Chip

This paper presents the fabrication and testing of electric cell-substrate impedance spectroscopy (ECIS) electrodes on a stretchable membrane. This is the first time when ECIS electrodes were fabricated on a stretchable substrate and ECIS measurements on mammalian cells exposed to cyclic strain of 10% were successfully demonstrated. A chemical was used to form strong chemical bond between gold electrodes of ECIS sensor and polymer membrane, which enable the electrodes keep good conductive ability during cyclic stretch. The stretchable membrane integrated with the ECIS sensor can simulate and replicate the dynamic environment of organism and enable the analysis of the cells activity involved in cells attachment and proliferation in vitro. Bovine aortic endothelial cells (BAEC) were used to evaluate the endothelial function influenced by mechanical stimuli in this research because they undergo in vivo cyclic physiologic elongation produced by the blood circulation in the arteries.

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