Myocyte shape regulates lateral registry of sarcomeres and contractility

Abstract

The heart actively remodels architecture in response to various physiological and pathological conditions. Gross structural change of the heart chambers is directly reflected at the cellular level by altering the morphological characteristics of individual cardiomyocytes. However, an understanding of the relationship between cardiomyocyte shape and the contractile function remains unclear. By using in vitro assays to analyze systolic stress of cardiomyocytes with controlled shape, we demonstrated that the characteristic morphological features of cardiomyocytes observed in a variety of pathophysiological conditions are correlated with mechanical performance. We found that cardiomyocyte contractility is optimized at the cell length/width ratio observed in normal hearts, and decreases in cardiomyocytes with morphological characteristics resembling those isolated from failing hearts. Quantitative analysis of sarcomeric architecture revealed that the change of contractility may arise from alteration of myofibrillar structure. Measurements of intracellular calcium in myocytes revealed unique characteristics of calcium metabolism as a function of myocyte shape. Our data suggest that cell shape is critical in determining contractile performance of single cardiomyocytes by regulating the intracellular structure and calcium handling ability.