Journal article
Reprogramming cardiomyocyte mechanosensing by crosstalk between integrins and hyaluronic acid receptors
Journal of biomechanics, v 45(5), pp 824-831
15 Mar 2012
PMID: 22196970
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The elastic modulus of bioengineered materials has a strong influence on the phenotype of many cells including cardiomyocytes. On polyacrylamide (PAA) gels that are laminated with ligands for integrins, cardiac myocytes develop well organized sarcomeres only when cultured on substrates with elastic moduli in the range 10kPa–30kPa, near those of the healthy tissue. On stiffer substrates (>60kPa) approximating the damaged heart, myocytes form stress fiber-like filament bundles but lack organized sarcomeres or an elongated shape. On soft (<1kPa) PAA gels myocytes exhibit disorganized actin networks and sarcomeres. However, when the polyacrylamide matrix is replaced by hyaluronic acid (HA) as the gel network to which integrin ligands are attached, robust development of functional neonatal rat ventricular myocytes occurs on gels with elastic moduli of 200Pa, a stiffness far below that of the neonatal heart and on which myocytes would be amorphous and dysfunctional when cultured on polyacrylamide-based gels. The HA matrix by itself is not adhesive for myocytes, and the myocyte phenotype depends on the type of integrin ligand that is incorporated within the HA gel, with fibronectin, gelatin, or fibrinogen being more effective than collagen I. These results show that HA alters the integrin-dependent stiffness response of cells in vitro and suggests that expression of HA within the extracellular matrix (ECM) in vivo might similarly alter the response of cells that bind the ECM through integrins. The integration of HA with integrin-specific ECM signaling proteins provides a rationale for engineering a new class of soft hybrid hydrogels that can be used in therapeutic strategies to reverse the remodeling of the injured myocardium.
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Details
- Title
- Reprogramming cardiomyocyte mechanosensing by crosstalk between integrins and hyaluronic acid receptors
- Creators
- Anant Chopra - Department of Biomedical Engineering, Drexel University, Philadelphia, PA, USAVictor Lin - Department of Cardiothoracic Surgery, Drexel University College of Med, Philadelphia, PA, USAAmanda McCollough - Glycosan Biosystems, Salt Lake City, UT, USASarah Atzet - Glycosan Biosystems, Salt Lake City, UT, USAGlenn D Prestwich - Glycosan Biosystems, Salt Lake City, UT, USAAndrew S Wechsler - Department of Cardiothoracic Surgery, Drexel University College of Med, Philadelphia, PA, USAMaria E Murray - Institute for Medicine and Engineering, University of Pennsylvania, 1010 Vagelos Laboratories, 3340 Smith Walk, Philadelphia, PA 19104, USAShaina A Oake - Institute for Medicine and Engineering, University of Pennsylvania, 1010 Vagelos Laboratories, 3340 Smith Walk, Philadelphia, PA 19104, USAJ Yasha Kresh - Department of Biomedical Engineering, Drexel University, Philadelphia, PA, USAPaul A Janmey - Institute for Medicine and Engineering, University of Pennsylvania, 1010 Vagelos Laboratories, 3340 Smith Walk, Philadelphia, PA 19104, USA
- Publication Details
- Journal of biomechanics, v 45(5), pp 824-831
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000302040800013
- Scopus ID
- 2-s2.0-84857650352
- Other Identifier
- 991014877700204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biophysics
- Engineering, Biomedical