Matrix nanotopography as a regulator of cell function

Kim, Deok Ho; Provenzano, Paolo P.; Smith, Chris; Levchenko, Andre

doi:10.1083/jcb.201108062

Cited by 535 publications

(503 citation statements)

References 119 publications

(174 reference statements)

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“…These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function [10][11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Capillary Force Lithography for Cardiac Tissue Engineering

Macadangdang

Lee

Carson

et al. 2014

JoVE

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Cardiovascular disease remains the leading cause of death worldwide 1 . Cardiac tissue engineering holds much promise to deliver groundbreaking medical discoveries with the aims of developing functional tissues for cardiac regeneration as well as in vitro screening assays. However, the ability to create high-fidelity models of heart tissue has proven difficult. The heart's extracellular matrix (ECM) is a complex structure consisting of both biochemical and biomechanical signals ranging from the micro-to the nanometer scale 2 . Local mechanical loading conditions and cell-ECM interactions have recently been recognized as vital components in cardiac tissue engineering [3][4][5] .A large portion of the cardiac ECM is composed of aligned collagen fibers with nano-scale diameters that significantly influences tissue architecture and electromechanical coupling 2 . Unfortunately, few methods have been able to mimic the organization of ECM fibers down to the nanometer scale. Recent advancements in nanofabrication techniques, however, have enabled the design and fabrication of scalable scaffolds that mimic the in vivo structural and substrate stiffness cues of the ECM in the heart [6][7][8][9] .Here we present the development of two reproducible, cost-effective, and scalable nanopatterning processes for the functional alignment of cardiac cells using the biocompatible polymer poly(lactide-co-glycolide) (PLGA) 8 and a polyurethane (PU) based polymer. These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function [10][11][12][13][14] .Using a nanopatterned (NP) silicon master as a template, a polyurethane acrylate (PUA) mold is fabricated. This PUA mold is then used to pattern the PU or PLGA hydrogel via UV-assisted or solvent-mediated capillary force lithography (CFL), respectively 15,16 . Briefly, PU or PLGA pre-polymer is drop dispensed onto a glass coverslip and the PUA mold is placed on top. For UV-assisted CFL, the PU is then exposed to UV radiation (λ = 250-400 nm) for curing. For solvent-mediated CFL, the PLGA is embossed using heat (120 °C) and pressure (100 kPa). After curing, the PUA mold is peeled off, leaving behind an ANFS for cell culture. Primary cells, such as neonatal rat ventricular myocytes, as well as human pluripotent stem cell-derived cardiomyocytes, can be maintained on the ANFS 2 . Video LinkThe video component of this article can be found at

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Section: Introductionmentioning

confidence: 99%

Capillary Force Lithography for Cardiac Tissue Engineering

Macadangdang

Lee

Carson

et al. 2014

JoVE

Self Cite

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“…Attempts have been made in developing more effective in vitro nanoscale devices to recapitulate in vivo ECM conditions (Kim et al, 2012b). Polymeric anisotropic nanopatterns promoted the differentiation of cardiac stem cells and myocardial regeneration in the infarcted rat heart (Kim et al, 2010;2012a).…”

Section: Nanodevices As Extracellular Matrix-mimicrymentioning

confidence: 99%

Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

Kim

Ahn

Chung

et al. 2013

Molecules and Cells

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Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnologybased materials and living cells in both in vitro and in vivo settings.

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“…For instance, recent studies have highlighted the importance of mechanical cues in regulating the above phenomenon [9]. Perhaps the most surprising result emerging from this research is that mechanical inputs can provide important differentiation cues and that these cues are not simply permissive, but instructive in nature [9][10][11]. In other words, the mechanical properties of the surrounding environment, such as matrix elasticity, can not only permit or enhance certain predefined differentiation outcomes but also determine which lineage is adopted by multipotent stem or precursor cells [8].…”

Section: Integrative Control Of Tissue Development and Regenerationmentioning

confidence: 99%

“…1A). Given this result, it was even more surprising that another mechanical cue, the defined nanoscale texture or nanotopography of the cell environment [11,28], mimicking the organization of the myocardial extracellular matrix, resulted in preferential differentiation of CDCs into cardiomyocytes [13] (Fig. 1A).…”

Section: Mechanical Cues In Cardiac Tissue Regenerationmentioning

confidence: 99%

Concise Review: Mechanotransduction via p190RhoGAP Regulates a Switch Between Cardiomyogenic and Endothelial Lineages in Adult Cardiac Progenitors

et al. 2014

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Mechanical cues can have pleiotropic influence on stem cell shape, proliferation, differentiation, and morphogenesis, and are increasingly realized to play an instructive role in regeneration and maintenance of tissue structure and functions. To explore the putative effects of mechanical cues in regeneration of the cardiac tissue, we investigated therapeutically important cardiosphere-derived cells (CDCs), a heterogeneous patient-or animal-specific cell population containing c-Kit 1 multipotent stem cells. We showed that mechanical cues can instruct c-Kit 1 cell differentiation along two lineages with corresponding morphogenic changes, while also serving to amplify the initial c-Kit 1 subpopulation. In particular, mechanical cues mimicking the structure of myocardial extracellular matrix specify cardiomyogenic fate, while cues mimicking myocardium rigidity specify endothelial fates. Furthermore, we found that these cues dynamically regulate the same molecular species, p190RhoGAP, which then acts through both RhoAdependent and independent mechanisms. Thus, differential regulation of p190RhoGAP molecule by either mechanical inputs or genetic manipulation can determine lineage type specification. Since human CDCs are already in phase II clinical trials, the potential therapeutic use of mechanical or genetic manipulation of the cell fate could enhance effectiveness of these progenitor cells in cardiac repair, and shed new light on differentiation mechanisms in cardiac and other tissues. STEM CELLS

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Matrix nanotopography as a regulator of cell function

Cited by 535 publications

References 119 publications

Capillary Force Lithography for Cardiac Tissue Engineering

Capillary Force Lithography for Cardiac Tissue Engineering

Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

Concise Review: Mechanotransduction via p190RhoGAP Regulates a Switch Between Cardiomyogenic and Endothelial Lineages in Adult Cardiac Progenitors

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