Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Poster Abstracts

26-POS Board 26 QUANTIFYING AND MECHANOSIGNALING IN HIPSC-CARDIOMYOCYTES IN HEALTH AND DISEASE Beth Pruitt ; 1 UCSB, BioE, Santa Barbara, CA, USA We combine microfabrication to control the ligands, stiffness, and morphology of biointerfaces to enable quantitative measurements of structure and mechanical function of cells through video analysis of cells patterned on microfabricated traction force microscopy devices. We use this workflow to manipulate and measure the mechanobiology of single cells to study maturation, remodeling, and functional changes of muscle cells in response to mechanical challenges, pharmacological treatments, or disease mutations. For example, we have used our platform to study Hypertrophic Cardiomyopathy (HCM) which is associated with thickening of the left ventricular wall, hypercontractility, and remodeling of the heart that ultimately reduces ventricular volume and pumping efficiency. HCM is characterized by changes in cellular level genotype and phenotype in the motor unit of the heart – the striated cardiac muscle cells known as cardiomyocytes. Using single cell mechanobiology studies, we examine how the effects of single point mutations propagate to change the contractile dynamics and cellular morphology (sarcomere spacing, spread area, myofibril alignment) of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). We micropattern islands of adhesive protein to constraining the spreading and alignment of hiPSC-CM on hydrogel substrates containing fluorescent microbeads as fiducial markers for traction force microscopy (TFM). We deploy substrate stiffnesses ranging from physiological (10 kPa) to heavily diseased/fibrotic (100 kPa) to test the role of increased “afterload” in functional phenotypes. We use image and video analysis to assess the contractile dynamics of the hiPSC-CM in terms of force, power, and velocities of relaxation and contraction.

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