3D Micropillars Guide the Mechanobiology of Human Induced Pluripotent Stem Cell‐Derived Cardiomyocytes

Palankar, Raghavendra; Glaubitz, Michael; Martens, Ulrike; Medvedev, Nikolay; Ehe, Marvin von der; Felix, Stephan B.; Münzenberg, Markus; Delcea, Mihaela

doi:10.1002/adhm.201500740

Cited by 12 publications

(13 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, Young's modulus of hiPSC-CMs is expected to be lower than that of primary cells. In fact, according to AFM-based measurements, the average apparent Young's modulus for adherent hiPSC-CMs has been reported to be between 0.3 kPa and 0.5 kPa [41,42]. Likewise, from our RT-DC measurements we derive an average Young's modulus for individual hiPSC-CMs of 1.25 ± 0.08 kPa.…”

Section: Discussionsupporting

confidence: 62%

Cardiomyocyte mechanodynamics under conditions of actin remodelling

Pires¹,

Shree²,

Manu³

et al. 2019

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

The mechanical performance of cardiomyocytes (CMs) is an important indicator of their maturation state and of primary importance for the development of therapies based on cardiac stem cells. As the mechanical analysis of adherent cells at high-throughput remains challenging, we explore the applicability of real-time deformability cytometry (RT-DC) to probe cardiomyocytes in suspension. RT-DC is a microfluidic technology allowing for real-time mechanical analysis of thousands of cells with a throughput exceeding 1000 cells per second. For CMs derived from human-induced pluripotent stem cells, we determined a Young's modulus of 1.25 ± 0.08 kPa which is in close range to previous reports. Upon challenging the cytoskeleton with cytochalasin D (CytoD) to induce filamentous actin depolymerization, we distinguish three different regimes in cellular elasticity. Transitions are observed below 10 nM and above 10 3 nM and are characterized by a decrease in Young's modulus. These regimes can be linked to cytoskeletal and sarcomeric actin contributions by CM contractility measurements at varying CytoD concentrations, where we observe a significant reduction in pulse duration only above 10 3 nM while no change is found for compound exposure at lower concentrations. Comparing our results to mechanical cell measurements using atomic force microscopy, we demonstrate for the first time to our knowledge, the feasibility of using a microfluidic technique to measure mechanical properties of large samples of adherent cells while linking our results to the composition of the cytoskeletal network. This article is part of a discussion meeting issue ‘Single cell ecology'.

show abstract

Section: Discussionsupporting

confidence: 62%

Cardiomyocyte mechanodynamics under conditions of actin remodelling

Pires¹,

Shree²,

Manu³

et al. 2019

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

show abstract

“…This technique can provide a quantitative force map of cardiomyocytes exerted to each pillar, offering a powerful tool for cardiac contractility studies with a high spatial resolution at the singlecell level. [120,122] Currently, most MPAs are made of PDMS substrate using soft lithography techniques. To enable cardiomyocytes to adhere to the tips of the micropillars, MPAs were functionalized with extracellular matrix protein.…”

Section: Micropillar Arrays (Mpas)mentioning

confidence: 99%

“…In recent years, a different method using the micropillar/micropost arrays (MPAs) has been utilized for measuring the contractile force of smooth muscle cells, [ 116,117 ] endothelial cells, [ 118 ] neural stem cells, [ 119 ] and cardiomyocytes. [ 120,121 ] This system relies on the array of compliant micropillars with constant controllable dimensions (diameter and height), and the contractions of attached cells bend the micropillars, whose deflections are observed by optical microscopy. Then the contractile forces exerted by cells can be calculated from the displacements of micropillars using beam bending theory.…”

Section: Contractile Force Detectionmentioning

confidence: 99%

Advances in Multidimensional Cardiac Biosensing Technologies: From Electrophysiology to Mechanical Motion and Contractile Force

Wei

Zhuang

et al. 2020

Small

View full text Add to dashboard Cite

Cardiovascular disease (CVD) is the number one killer in the world. According to the World Health Organization (WHO) estimation, about 17.9 million people died from CVD each year, accounting for 31% of all deaths worldwide. [1] Among these deaths, about 7.4 million died from coronary heart disease, while 6.7 million from a stroke. According to China cardiovascular disease report in 2018, [2] around 290 million people suffer from CVD, including 13 million strokes, 11 million coronary heart disease, 5 million pulmonary heart disease, 4.5 million heart failure, 2.5 million rheumatic heart disease, 2 million congenital heart disease, and 270 million hypertension. Cardiovascular disease was also the leading cause of all death in rural and urban areas, with 45.01% in rural areas and 42.61% in urban areas. According to heart disease and stroke statistics from the American Heart Association (AHA) in 2018, [3] around 92.1 million American adults have a certain form of cardiovascular disease or suffer from stroke sequelae. CVD killed 836546 Americans in 2015. Coronary heart disease was the leading cause (43.8%) of death in CVD, followed by stroke (16.8%), heart failure (9.0%), hypertension (9.4%), arterial disease (3.1%) and other cardiovascular diseases (17.9%). According to the European cardiovascular disease statistics in 2017, [4] around 3.9 million people died from CVD each year, which accounts for 45% of all deaths in Europe. Ischemic heart disease (IHD) and stroke are the main forms of CVD in Europe. Among all deaths in Europe each year, IHD is the leading single cause of mortality, responsible for 19% and 20% among men and women, while stroke is the second most common single cause of death, accounting for 9% in men and 13% in women. Therefore, the prevention and treatment of CVD have aroused extensive public concern worldwide. Moreover, cardiac toxicity induced by drugs has been the main cause of the withdrawal from the market and drugs attrition during the last decades. [5,6] On the one hand, drug-induced cardiotoxicity will also threaten people's health, even life. For example, acute arrhythmia can lead to sudden death, while Cardiovascular disease is currently a leading killer to human, while druginduced cardiotoxicity remains the main cause of the withdrawal and attrition of drugs. Taking clinical correlation and throughput into account, cardiomyocyte is perfect as in vitro cardiac model for heart disease modeling, drug discovery, and cardiotoxicity assessment by accurately measuring the physiological multiparameters of cardiomyocytes. Remarkably, cardiomyocytes present both electrophysiological and biomechanical characteristics due to the unique excitation-contraction coupling, which plays a significant role in studying the cardiomyocytes. This review mainly focuses on the recent advances of biosensing technologies for the 2D and 3D cardiac models with three special properties: electrophysiology, mechanical motion, and contractile force. These high-performance multidimensional cardiac models are popular and ef...

show abstract

“…Another approach to improve MEA microfabrication would be to create a substrate that integrates topography that can guide network formation and can simultaneously stimulate neuronal maturation. A number of studies have demonstrated the ability of topography to direct cell growth, control cell shape and polarity, and affect differentiation and proliferation [7][8][9]. In general, the response to topography depends on the substrate and the specific surface features that are being introduced and even more on the cell type under examination.…”

Section: Introductionmentioning

confidence: 99%

Topographical Guidance of PSC-Derived Cortical Neurons

Terryn

Welkenhuysen

Krylychkina

et al. 2018

Journal of Nanomaterials

View full text Add to dashboard Cite

Background and Aims. Human pluripotent stem cell- (PSC-) derived neurons are increasingly used in the study of neurodevelopmental and neurodegenerative diseases. Electrophysiological activity is a crucial and defining function of these neurons. Patch clamping and the more recently developed multielectrode arrays are used to evaluate this complex function. In this study, we assess the effect of topography on PSC-derived neurons as a baseline for the development of next-generation silicon oxide substrates (in direct relation to MEA fabrication) that integrate topography as a means to guide network formation and stimulate differentiation. Methods. Human PSC was differentiated towards cortical neurons and seeded on a silicon micropatterned substrate to screen for topographic guidance and improved neurite outgrowth. We next developed customized micropillar and microgroove substrates to further assess the effect of topography on human cortical neurons. Immunocytochemistry and morphological analyses were used to track neuron differentiation and guidance. Results. Microgroove and micropillar substrates appeared to support the differentiation of human stem cell-derived cortical neurons, promoted neurite outgrowth, and facilitated contact guidance. In contrast to flat surfaces, topography also appeared to limit the number of NESTIN positive neuronal progenitor cells present in the culture. Conclusion. We describe the topographical preferences of human PSC-derived cortical neurons, on neurite outgrowth and guidance. Embedding topography in silicon substrates may be an effective approach to direct and improve neuronal network formation. We propose to integrate topography in multielectrode arrays as a practical method to shape the neuro-electronic interface.

show abstract

3D Micropillars Guide the Mechanobiology of Human Induced Pluripotent Stem Cell‐Derived Cardiomyocytes

Cited by 12 publications

References 41 publications

Cardiomyocyte mechanodynamics under conditions of actin remodelling

Cardiomyocyte mechanodynamics under conditions of actin remodelling

Advances in Multidimensional Cardiac Biosensing Technologies: From Electrophysiology to Mechanical Motion and Contractile Force

Topographical Guidance of PSC-Derived Cortical Neurons

Contact Info

Product

Resources

About