The Matrix Stiffness Method—Part 1: Beams and Rectangular Frames

ABSTRACTUnderstanding factors affecting cell invasion influences the design of engineered constructs for tissue regeneration. The objective of this work was to investigate the effect of matrix stiffness on invasion of tumor cells through a synthetic hydrogel with well-defined properties. A novel star acrylate-functionalized polyethylene glycol-co-lactide (SPELA) macromer was synthesized to produce hydrogels with well-defined water content, elastic modulus, degree of crosslinking and hydrophilicity. The hydrogel was formed by photo-polymerization of the macromer with or without integrin-binding cell adhesive RGD peptide. Cell invasion experiments were carried out in a transwell with SPELA hydrogel as the invading matrix and 4T1 mouse breast cancer cells. The invading cells on the lower membrane side were counted with an inverted fluorescent microscope. The concentration of SPELA macromer ranged from 10-25 wt% and that of RGD ranged from 1x10-4 to 1x10-2 M. The shear modulus of the hydrogel varied from 200 Pa to 25 kPa as the SPELA concentration increased from 10 to 25 wt%. Cell invasion slightly increased with increasing RGD concentration. However, RGD concentration >1% resulted in a significant decrease in cell migration. As the matrix stiffness increased from 0.15 to 0.4, 3, 5, 6, 14, and 25 kPa the invasion rate decreased from 18.0 to 5.5, 6, 5.7, 5.2, 1.5, and 1.0 cells/mm2/h, respectively. There was a sharp decrease in invasion rate for matrix stiffness greater than 10 kPa. Results demonstrate that matrix stiffness plays a major role in invasion of tumor cell through a gelatinous matrix.

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The Effect of Iron Oxide on the Mechanical and Ageing Properties of Y-TZP Ceramic

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.701.225 ◽

2016 ◽

Vol 701 ◽

pp. 225-229 ◽

Cited By ~ 6

Author(s):

Sivanesan Sivakumar ◽

Hsien Loong Teow ◽

Ramesh Singh ◽

Ali Niakan ◽

Nobuyuki Mase

Keyword(s):

Fracture Toughness ◽

Iron Oxide ◽

Bulk Density ◽

Phase Stability ◽

Vickers Hardness ◽

Tetragonal Phase ◽

Superheated Steam ◽

Matrix Stiffness ◽

Sintering Aid ◽

The Matrix

A small amount of iron oxide (Fe2O3) was added to the commercially available 3 mol% Y-TZP as a sintering aid over a temperature range of 1250°C to 1500°C. Sintered samples were then evaluated to determine the bulk density, Vickers hardness, and fracture toughness. In addition, hydrothermal ageing experiments to determine the tetragonal phase stability were performed on selected sintered samples in superheated steam at 180°C / 10 bar for up to 24 hours. Based on the work carried out, it was revealed that additions of Fe2O3 particularly 0.3 wt% was indeed beneficial in aiding densification, improving the matrix stiffness and hardness when compared to undoped Y-TZP sintered at temperatures below 1350°C. Addition of Fe2O3 was found to have negligible effects on the fracture toughness of all samples with the exception of the 0.5 and 1 wt% doped Y-YZP sintered above 1400°C. Hydrothermal ageing resistance of Y-TZP was found to be enhanced with the addition of Fe2O3 in the Y-TZP matrix.

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A simplified matrix stiffness method for analysis of composite and prestressed beams

Steel and Composite Structures ◽

10.12989/scs.2017.24.1.053 ◽

2017 ◽

Vol 24 (1) ◽

pp. 53-63 ◽

Cited By ~ 1

Author(s):

Biljana Deretic-Stojanovic ◽

Svetlana M. Kostic

Keyword(s):

Matrix Stiffness ◽

Stiffness Method ◽

Prestressed Beams

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Extracellular Matrix Stiffness Modulates Microvascular Morphology During Early Sprouting Angiogenesis In Vitro

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206782 ◽

2009 ◽

Cited By ~ 2

Author(s):

Laxminarayanan Krishnan ◽

Urs Utzinger ◽

Steve Maas ◽

Shawn Reese ◽

Jeffrey A. Weiss ◽

...

Keyword(s):

Matrix Stiffness ◽

Matrix Rigidity ◽

Cellular Functions ◽

Sprouting Angiogenesis ◽

Vascular Morphology ◽

The Matrix ◽

Extracellular Matrix Stiffness ◽

Local Stiffness ◽

Matrix Orientation

Sprouting angiogenesis is associated with changes in matrix stiffness[1]. Neovessel growth and morphology are in turn affected by the changes in matrix orientation or forces acting on the matrix[2]. Matrix rigidity influences the formation of cord like structures[3, 4] and could play a role in development of tissue specific vascular morphology or inhibit cellular functions in diseases. The effect of matrix stiffness on neovessel growth from preformed vasculature has not been examined. Matrix stiffness could be increased both by an increase in matrix density[5] as well as increased crosslink formation, as in hyperglycemia[6]. It is thus essential to first identify the effect of increase in local stiffness alone, in the absence of artificially induced crosslinks, which may interfere with matrix orientation. Our aim is to characterize changes in early angiogenesis associated with ECM of different densities and relate these to changes in matrix orientation.

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An Active Chemo-mechanical Model to Predict Adhesion and Microenvironmental Regulation of 3D Cell Shapes

10.1101/2020.01.07.897405 ◽

2020 ◽

Cited By ~ 1

Author(s):

Xingyu Chen ◽

Veronika te Boekhorst ◽

Eoin McEvoy ◽

Peter Friedl ◽

Vivek B. Shenoy

Keyword(s):

Cell Types ◽

Matrix Stiffness ◽

Collagen Gels ◽

Collagen Matrices ◽

Feedback Model ◽

3D Microenvironment ◽

The Matrix ◽

Cell Shapes ◽

Quantitative Understanding ◽

3D Collagen

AbstractCell shapes are known to regulate cytoskeletal organization, stiffness and the ability of cells to migrate and proliferate. Yet a quantitative understanding of the fundamental biochemical and biophysical mechanisms that determine the cell shapes is currently not available. In this study, we developed a chemo-mechanical feedback model to predict how adhesions and the properties of the 3D microenvironment regulate cell shapes. We find that the cells in 3D collagen matrices remain round or adopt an elongated shape depending on the density of active integrins, the level of contractility regulated by mechanosensitive signaling pathways and the density and mechanics of the matrix. While the formation of actin fibers that run along the cell body mediated by integrins and matrix stiffness drive elongation of cells, the cortical and membrane tension resist elongation. Based on the competition between these mechanisms, we derive phase diagrams for cell shape in the space spanned by the density of active adhesions and the level of biochemical signaling that controls contractility. Our predictions are validated by studying the shapes of HT1080 cells cultured in collagen gels of varying densities and using pharmacological treatments to regulate adhesions and contractility. The predictions of the model are found to be in excellent agreement with our experiments and data reported on a number of cell types in the literature.

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Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer

Nature Communications ◽

10.1038/s41467-021-27220-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Pauliina M. Munne ◽

Lahja Martikainen ◽

Iiris Räty ◽

Kia Bertula ◽

Nonappa ◽

...

Keyword(s):

Breast Cancer ◽

Cultured Cells ◽

Ex Vivo ◽

Therapeutic Interventions ◽

Preclinical Model ◽

Matrix Stiffness ◽

Breast Cancers ◽

Ex Vivo Model ◽

Major Barrier ◽

The Matrix

AbstractBreast cancer is now globally the most frequent cancer and leading cause of women’s death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.

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