A Generative AI Framework to Predict Cardiomyocyte Contraction Function From Single Static Images

Understanding how cardiomyocyte structure governs contractile function is fundamental to cardiac biology and disease modeling, yet current approaches rely on time‐resolved imaging and computationally intensive analysis. Here, we present a generative artificial intelligence (AI) framework that directly predicts contractile behavior of human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) from single static images. Our approach integrates a U‐Net‐based generator with a patch‐based generative adversarial network (GAN) discriminator to translate morphological and sarcomere structural features into pixel‐resolved contraction heatmaps. To further enhance performance and generalizability, we incorporated synthetic cell–function pairs generated via a StyleGAN2 framework, improving prediction accuracy and perceptual similarity. Region‐specific and whole‐cell analyses revealed that AI predictions capture biologically meaningful structure–function relationships, with sarcomere organization strongly associated with both contractile output and prediction fidelity. Reconstruction error emerged as an interpretable metric reflecting localized inefficiencies in sarcomere‐to‐contraction coupling. Together, this framework establishes a scalable, interpretable strategy for inferring cardiomyocyte function from static morphology, eliminating the need for time‐lapse imaging, and positions generative AI as a powerful tool for bridging cellular structure and function to advance high‐throughput phenotyping and in vitro cardiac modeling.