The giant titin: how to evaluate its role in cardiomyopathies

Figures

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  Fig. 1. Schematic drawing of the sarcomere. Each titin molecule (black) spans half the sarcomere from the Z-disc to the M-band, linking thin filaments (bold black) and thick filaments (grey). The positions of I-band and A-band are also indicated. Bottom: The amino-terminus (N) and the carboxy-terminus (C) of an individual titin molecule are marked (bottom of figure). The A-band portion of titin as a hotspot for DCM-causing variants is indicated. For more detailed schemes of titin domain structure please see Bang et al. (2001), Lange et al. (2006)

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  Fig. 2. Immature phenotype of iPSC-CM in conventional 2D cultures: Normal Kolf2 iPSC (Streeter et al. 2017) were differentiated into iPSC-CMs using standard methods (Burridge et al. 2015) and plated on day 20 on different substrates: matrigel coated glass (top left), matrigel coated hydrogel (top right, 7 kPa) and nano-patterned matrigel coated hydrogel (bottom left, see Ribeiro et al. (2015)). 30 days after induction of differentiation, cells were fixed and sarcomeric structures visualised with an antibody direct against alpha-actinin (EA53, Sigma). For comparison, an isolated mouse cardiomyocyte stained with the same antibody is shown (bottom right). Scale bars represent 10 microns