Gain-of-function Mutation in Ubiquitin Ligase KLHL24 Causes Desmin Degradation and Dilatation in hiPSC-Derived Engineered Heart Tissues

Mathilde C.S.C. Vermeer, Maria C. Bolling, Jacqueline M. Bliley, Karla F. Arevalo Gomez, Mario G. Pavez-Giani, Duco Kramer, Pedro H. Romero-Herrera, B. Daan Westenbrink, Gilles F.H. Diercks, Maarten P. van den Berg,1 Adam W. Feinberg, Herman H.W. Silljé, and Peter van der Meer are co-authors on a recent publication in The Journal of Clinical Investigation titled “Gain-of-function Mutation in Ubiquitin Ligase KLHL24 Causes Desmin Degradation and Dilatation in hiPSC-Derived Engineered Heart Tissues.” Here, the authors use the dynamically loaded engineered heart tissue (dyn-EHT) system to model dilated cardiomyopathy in patients with a KLHL24 mutation.

Read the article in The Journal of Clinical Investigation.


Dynamic Loading of Human Engineered Heart Tissue Enhances Contractile Function and Drives a Desmosome-linked Disease Phenotype

Jacqueline M. Bliley, Mathilde C. S. C. Vermeer, Rebecca M. Duffy, Ivan Batalov, Duco Kramer, Joshua W. Tashman, Daniel J. Shiwarski, Andrew Lee, Alexander S. Teplenin, Linda Volkers, Brian Coffin, Martijn F. Hoes, Anna Kalmykov, Rachelle N. Palchesko, Yan Sun, Jan D. H. Jongbloed, Nils Bomer, Rudolf A. de Boer, Albert J. H. Suurmeijer, Daniel A. Pijnappels, Maria C. Bolling, Peter van der Meer*, and Adam W. Feinberg are co-authors on our recent publication in Science Translational Medicine titled “Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype.” Here, we use a novel dynamic engineered heart tissue (dyn-EHT) system to model arrhythmogenic cardiomyopathy.

Read the article in Science Translational Medicine.


Engineering Aligned Human Cardiac Muscle Using Developmentally Inspired Fibronectin Micropatterns

Ivan Batalov, Quentin Jallerat, Sean Kim, Jacqueline Bliley and Adam W. Feinberg are co-authors on our recent paper published in Nature Scientific Reports titled “Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns.” Here, we sought to use developmentally inspired cardiac micropatterns to better understand cardiomyocyte alignment.

Read the article in Nature Scientific Reports


Fibronectin-Based Nanomechanical Biosensors to Map 3D Strains in Live Cells and Tissue

Dan Shiwarski, Josh Tashman, Alkiviadis Tsamis, Jaci Bliley, Malachi Blundon, Edgar Aranda-Michel, Quentin Jallerat, John Szymanski, Brooke McCartney and Adam Feinberg are co-authors on our recent article in Nature Communications entitled “Fibronectin-Based Nanomechanical Biosensors to Map 3D Strains in Live Cells and Tissues.” The ability to measure strain in cells and tissues in vitro with minimal perturbation and at high spatial resolution has proven challenging. Here, we have developed a fluorescently-labelled nanomechanical biosensor (NMBS) made of a fibronectin square lattice mesh with tunable resolution that can be applied to the surface of cells and tissues to enable direct quantification and mapping of strain over time. Additionally, we have released an open-source MATLAB and Imaris biomechanics software package to map and quantify 3D surface strain, cardiomyocyte beat frequency, and area dilation from live fluorescence imaging data. Accompanying the manuscript is a published protocol detailing the step-by-step NMBS fabrication process.

Read the article at Nature Communications


FRESH 3D Bioprinting a Full-Size Model of the Human Heart

Eman Mirdamadi, Josh Tashman, Dan Shiwarski, Rachelle Palchesko, and Adam Feinberg are co-authors on our recent article in ACS Biomaterials Science & Engineering entitled “FRESH 3D Bioprinting a Full-Size Model of the Human Heart.” In the article, we demonstrate the FRESH platform’s capabilities in printing acellular, full-sized human heart models from alginate, which possesses similar mechanical properties to cardiac tissue, enabling surgeons to one day use our models for realistic surgical simulation.

Read the article at ACS Biomaterials Science & Engineering

“Patterning on Topography for Generation of Cell Culture Substrates with Independent Nanoscale Control of Chemical and Topographical Extracellular Matrix Cues”

Emily Sevcik, John Szymanksi and Quentin Jallerat are co-authors on our recent article in Current Protocols in Cell Biology entitled “Patterning on Topography for Generation of Cell Culture Substrates with Independent Nanoscale Control of Chemical and Topographical Extracellular Matrix Cues.” In the article we provide detailed methods on how to perform our Patterning on Topography (PoT) technology to independently pattern extracellular matrix proteins on topographically complex surfaces for studying cell-material interactions.

Read the article at Current Protocols in Cell Biology

“Stretch-dependent changes in molecular conformation in fibronectin nanofibers”

John Szymanksi, Emily Sevcik and Kairui Zhang are co-authors on our recent article in Biomaterials Science entitled “Stretch-dependent changes in molecular conformation in fibronectin nanofibers.” This article is part of the Biomaterials Science Emerging Investigators 2017 issue of the journal. In the article we used AFM imaging of fibronectin nanofibers over a wide range of deformations to understand how reversible molecular unfolding contributes to the mechanical properties of extracellular matrix proteins.

Read the article at Biomaterials Science

“Measuring the Poisson’s Ratio of Fibronectin Using Engineered Nanofibers”

John Szymanksi and Kairui Zhang are co-authors on our recent article in Scientific Reports entitled “Measuring the Poisson’s Ratio of Fibronectin Using Engineered Nanofibers.” This article used AFM imaging of fibronection nanofibers over a wide range of deformations to show that volume is conserved, thus behaving as an elastic material with a Poisson’s ratio of ~0.5.

Read the article at Scientific Reports

“3D Printing PDMS Elastomer in a Hydrophilic Support Bath via Freeform Reversible Embedding”

TJ Hinton, Andrew Hudson, Kira Pusch and Andrew Lee are co-authors on our recent article in ACS Biomaterials Science & Engineering entitled “3D Printing PDMS Elastomer in a Hydrophilic Support Bath via Freeform Reversible Embedding.” This article describes a new technique termed Freeform Reversible Embedding (FRE) to 3D print polydimethysiloxane (PDMS) elastomer such as Sylgard 184 in complex 3D structures within a hydrophilic Carbopol support. Unique is the ability to 3D print PDMS that takes hours to days to cure, demonstrating the capability to 3D print fluidic materials and decoupling the gelation and curing of the polymer from its ability to be 3D printed.

Read the article at ACS Biomaterials Science & Engineering