2D Heart Models
Tunable Microenvironments for Robust 2D Cardiac Assays
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Cardiomyocyte maturation assay
Functional iPSC induced cardiopycyte fibers
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"3D" Cardiomyocyte maturation assay
Assessing the beating of iPSC-CMs
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Durotaxis and haptotaxis assay
Control of substrate stiffness
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Quantification of forces appiled by cells on the matrix
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Quantification of beating force of single cardiomyocyte cells
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Functional maturation of pacemaker cells
CARDIOMYOCYTES MATURATION ASSAY
Functional iPSC induced cardiomyocyte fibers
4Dcell technology
SmartPattern Technology
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Read-outs
Beating frequency, observation of sarcomeres
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Standard culture limitation
In standard cultures, cardiomyocytes derived from pluripotent stem cells have random shapes, are not organized thus showing immature properties.
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Cardiomyocyte maturation assay
When cultured in a substrate with line adhesive cues, cardiomyocytes acquire elongated shapes, which regulates cell contractility and establishes and maintains myofibril alignment and an improved and regular cell beating.
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Example
Organization of cardiomyocytes in line patterns [1], and effect of myofibril alignment in contractility forces.
hPSC-CM non patterned (left image) and on line micropatterns (right image) imaged by fluorescence microscopy. Dussaud S., Jouve C., Hulot J.S., 2018. These images were obtained through the courtesy of Professor Hulot (Hôpital Européen Georges-Pompidou) and his team, using 4Dcell products.
"3D" CARDIOMYOCYTES MATURATION ASSAY
Functional iPSC induced cardiomyocyte fibers
4Dcell technology
SmartGel Coverslip
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Read-outs
Cardiac muscle structure observation and contractility force measurement
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Standard culture limitation
In standard cultures, cardiomyocytes derived from pluripotent stem cells have random shapes and are not organized thus showing immature properties.
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"3D" Cardiomyocyte maturation assay
When cultured on 3D gels, hiPSC-CMs better mimic the real cardiac muscle structure and functions, thus leading to a more efficient maturity of iPSC-CMs.
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Example
Using a microgroove-patterned hydrogel, cardiomyocytes are organized for a better cell characterization (A). In addition, when comparing unpatterned cells with patterned ones on different groove sizes, the contraction performance is increased with the cells confinement (B)(C).
References
DUROTAXIS AND HAPTOTAXIS ASSAY
Control of substrate stiffness
4Dcell technology
SmartPillar Coverslip​
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Read-outs
Durotaxis, haptotaxis, substrate stiffness control
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Standard culture limitation
Cell migration plays a major role in many fundamental biological processes. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. However, it is difficult in a standard Petri dish to establish a stiffness gradient.
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Example
TRACTION FORCE ASSAY
Quantification of forces appiled by cells on the matrix
4Dcell technology
SmartPillar Coverslips​
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Read-outs
Traction forces and cell cortex contraction measurement, migration assays with substrate stiffness control
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Standard culture limitation
Cells are plated on an elastic gel containing fluorescent beads. Cellular forces are measured by the quantification of the displacement of fluorescent beads embedded in the elastic gel that is then converted in forces. However, this system induces limitation as forces propagate through this continuous elastic substrate making the contractility measurement less specific.
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Traction force assay
Using 4Dcell’s assay, a substrate consisting of PDMS micropillars, the forces applied by the cell are deduced from the micropillar apex displacement. The deflections of the micropillars, up to tens of nanometers can be measured, lead to a reliable force measurement of the order of 1 nN, enabling to plot a map of forces.
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Example
4Dcell SmartPillars
Fibroblasts in micropillars substrate (1)
Fibroblasts on µFSA substrate (2)
(A) Actin filaments of fibroblasts
(B) Actin filaments merged with image of µFSA substrate coated with fibronectin (Red)
SINGLE CARDIOMYOCYTES CONTRACTILITY FORCE
Functional iPSC induced cardiomyocyte fibers
4Dcell technology
SmartPillar Coverslips​
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Read-outs
Uniaxial Contraction Force, Analysis of Calcium Transients coupled to force measurements.
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Standard culture limitation
When hESC-Cardiomyocyes are cultured in standard conditions, i.e., in 2D monolayers of cells, these are organized in a complete random way. Therefore, it is not possible to precisely quantify the uniaxial force generated by the beating of a single cardiomyocyte cell.
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Single cardiomyocyte contractility force assay benefits
In this assay, derived cardiomyocytes attach to rectangular cell-adhesive areas, which induce cell elongation and promote suspended cell anchoring between two adjacent micropillars. The contractility force assay enables in vitro reproduction of excitation−contraction coupling effect responsible for the beating of CMs.
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Example
Quantification of calcium transients (activation of calcium-sensitive contractile proteins) and simultaneous measurement of cell contraction and force generation (analysis of pillars deflection) in hESC-Cardiomyocytes [1].
PACEMAKER CELL REGULATION
Functional maturation for enhanced and rhythmic electrical activity
4Dcell technology
SmartGel Coverslip
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Read-outs
Constrain of cell size in a substrate of a defined stiffness, functional electrical properties preservation.
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Standard culture limitation
Cardiac pacemaker cells undergo a series of cytoarchitectural patterning events during cardiogenesis that are critical for proper electrical excitability. Cell size regulation, which is scarcely under control in standard cell culture conditions, is crucial for their functional maturation.
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Cardiac pacemaker cells cytoarchitecture regulation assay
Maintenance of small cell size is beneficial for preserving the potential for high-rate and rhythmic activity in cardiac pacemaker cells.
Example
Regulation of cardiac pacemaker cell (CPC) size on 50 kPa polyacrylamide gels with round microwells [1].
CPC size was constrained over the culture period on 50 kPa micropatterned (MP) gels. Maintaining small cell size preserved function, as revealed by calcium transient rate quantification.