Nanomagnetic actuation of receptor-mediated signal transduction

Mannix, Robert; Kumar, Sanjay; Cassiola, Flávia; Montoya-Zavala, Martín; Feinstein, Efraim; Prentiss, Mara; Ingber, Donald E.

doi:10.1038/nnano.2007.418

Cited by 298 publications

(276 citation statements)

References 23 publications

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“…The impact of these nanotopographical cues on cell and tissue function, however, is far from completely understood. Preliminary studies of nanometer scale cell-biomaterial interaction indicate the potential importance and impact of sub-micron topographical cues for cell signaling 27 , adhesion [28][29][30] , growth 31 , and differentiation 32,33 . However, due to the difficulty in developing reproducible and scalable nanofabricated substrates, such studies could not reproduce the multi-scale cellular effects of the complex in vivo ECM environment.…”

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

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“…13 Magneto-mechanical actuation has been used as an effective method to introduce mechanical stimulation to single cells in studies of mechanotransduction. 11,[14][15][16][17][18][19] The extension of this technique to microtissues in the current study enables simultaneous measurement of both the contractile force and the tissue stiffness. Using this integrated magnetic microtissue tester (MMT) system, we decoupled the cell and ECM contributions to the contraction force and the stiffness of microtissues subjected to short culture periods (up to three days).…”

Section: Introductionmentioning

confidence: 99%

Magnetic approaches to study collective three-dimensional cell mechanics in long-term cultures (invited)

Zhao

Boudou

Wang

et al. 2014

Journal of Applied Physics

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Contractile forces generated by cells and the stiffness of the surrounding extracellular matrix are two central mechanical factors that regulate cell function. To characterize the dynamic evolution of these two mechanical parameters during tissue morphogenesis, we developed a magnetically actuated micro-mechanical testing system in which fibroblast-populated collagen microtissues formed spontaneously in arrays of microwells that each contains a pair of elastomeric microcantilevers. We characterized the magnetic actuation performance of this system and evaluated its capacity to support long-term cell culture. We showed that cells in the microtissues remained viable during prolonged culture periods of up to 15 days, and that the mechanical properties of the microtissues reached and maintained at a stable state after a fast initial increase stage. Together, these findings demonstrate the utility of this microfabricated bio-magneto-mechanical system in extended mechanobiological studies in a physiologically relevant 3D environment. V C 2014 AIP Publishing LLC.

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“…In this context, magnetic actuation of nanoparticles provides a novel strategy for controlling cells that is complementary to genetic, chemical and optogenetic tools 14 . For instance, recent key experiments have demonstrated the magnetic actuation of signalling pathways using nanoparticles conjugated to antibodies by inducing the clustering of extracellular receptors 15,16 or through endocytic internalization 17 . In these studies, nanoparticles are no longer passive reporters of biomolecules, but on interaction with a magnetic field actuate a biological response.…”

mentioning

confidence: 99%

Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles

et al. 2013

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Decisions on the fate of cells and their functions are dictated by the spatiotemporal dynamics of molecular signalling networks. However, techniques to examine the dynamics of these intracellular processes remain limited. Here, we show that magnetic nanoparticles conjugated with key regulatory proteins can artificially control, in time and space, the Ran/RCC1 signalling pathway that regulates the cell cytoskeleton. In the presence of a magnetic field, RanGTP proteins conjugated to superparamagnetic nanoparticles can induce microtubule fibres to assemble into asymmetric arrays of polarized fibres in Xenopus laevis egg extracts. The orientation of the fibres is dictated by the direction of the magnetic force. When we locally concentrated nanoparticles conjugated with the upstream guanine nucleotide exchange factor RCC1, the assembly of microtubule fibres could be induced over a greater range of distances than RanGTP particles. The method shows how bioactive nanoparticles can be used to engineer signalling networks and spatial self-organization inside a cell environment.

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Nanomagnetic actuation of receptor-mediated signal transduction

Cited by 298 publications

References 23 publications

Capillary Force Lithography for Cardiac Tissue Engineering

Capillary Force Lithography for Cardiac Tissue Engineering

Magnetic approaches to study collective three-dimensional cell mechanics in long-term cultures (invited)

Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles

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