PMID- 31719889 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220414 IS - 1865-5025 (Print) IS - 1865-5033 (Electronic) IS - 1865-5025 (Linking) VI - 11 IP - 5 DP - 2018 Oct TI - Microenvironmental Modulation of Calcium Wave Propagation Velocity in Engineered Cardiac Tissues. PG - 337-352 LID - 10.1007/s12195-018-0522-2 [doi] AB - INTRODUCTION: In the myocardium, rapid propagation of action potentials and subsequent calcium waves is critical for synchronizing the contraction of cardiac myocytes and maximizing cardiac output. In many pathological settings, diverse remodeling of the tissue microenvironment is correlated with arrhythmias and decreased cardiac output, but the precise impact of tissue remodeling on propagation is not completely understood. Our objective was to delineate how multiple features within the cardiac tissue microenvironment modulate propagation velocity. METHODS: To recapitulate diverse myocardial tissue microenvironments, we engineered substrates with tunable elasticity, patterning, composition, and topography using two formulations of polydimethylsiloxane (PDMS) micropatterned with fibronectin and gelatin hydrogels with flat or micromolded features. We cultured neonatal rat ventricular myocytes on these substrates and quantified cell density, tissue alignment, and cell shape. We used a fluorescent calcium indicator, high-speed microscopy, and newly-developed analysis software to record and quantify calcium wave propagation velocity (CPV). RESULTS: For all substrates, tissue alignment and cell aspect ratio were higher in aligned compared to isotropic tissues. Isotropic CPV and longitudinal CPV were similar across conditions, but transverse CPV was lower on micromolded gelatin hydrogels compared to micropatterned soft and stiff PDMS. In aligned tissues, the anisotropy ratio of CPV (longitudinal CPV/transverse CPV) was lower on micropatterned soft PDMS compared to micropatterned stiff PDMS and micromolded gelatin hydrogels. CONCLUSION: Propagation velocity in engineered cardiac tissues is sensitive to features in the tissue microenvironment, such as alignment, matrix elasticity, and matrix topography, which may underlie arrhythmias in conditions with pathological tissue remodeling. CI - (c) Biomedical Engineering Society 2018. FAU - Petersen, Andrew P AU - Petersen AP AD - Department of Biomedical Engineering, Laboratory for Living Systems Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089 USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 FAU - Lyra-Leite, Davi M AU - Lyra-Leite DM AD - Department of Biomedical Engineering, Laboratory for Living Systems Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089 USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 FAU - Ariyasinghe, Nethika R AU - Ariyasinghe NR AD - Department of Biomedical Engineering, Laboratory for Living Systems Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089 USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 FAU - Cho, Nathan AU - Cho N AD - Department of Biomedical Engineering, Laboratory for Living Systems Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089 USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 FAU - Goodwin, Celeste M AU - Goodwin CM AD - Department of Biomedical Engineering, Laboratory for Living Systems Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089 USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 FAU - Kim, Joon Young AU - Kim JY AD - Department of Biomedical Engineering, Laboratory for Living Systems Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089 USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 FAU - McCain, Megan L AU - McCain ML AUID- ORCID: 0000-0003-1908-6783 AD - Department of Biomedical Engineering, Laboratory for Living Systems Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089 USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 AD - Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA USA. ISNI: 0000 0001 2156 6853. GRID: grid.42505.36 LA - eng PT - Journal Article DEP - 20180417 PL - United States TA - Cell Mol Bioeng JT - Cellular and molecular bioengineering JID - 101468590 PMC - PMC6816715 OTO - NOTNLM OT - Calcium imaging OT - Cardiac myocytes OT - Elastic modulus OT - Extracellular matrix OT - Microcontact printing OT - Microfabrication OT - Micromolding EDAT- 2018/04/17 00:00 MHDA- 2018/04/17 00:01 PMCR- 2019/04/17 CRDT- 2019/11/14 06:00 PHST- 2018/01/18 00:00 [received] PHST- 2018/04/09 00:00 [accepted] PHST- 2019/11/14 06:00 [entrez] PHST- 2018/04/17 00:00 [pubmed] PHST- 2018/04/17 00:01 [medline] PHST- 2019/04/17 00:00 [pmc-release] AID - 522 [pii] AID - 10.1007/s12195-018-0522-2 [doi] PST - epublish SO - Cell Mol Bioeng. 2018 Apr 17;11(5):337-352. doi: 10.1007/s12195-018-0522-2. eCollection 2018 Oct.