Force generation of cardiomyocytes in engineered environments

Cardiomyocyte contraction is crucial for heart function, but it declines after heart injury or fibrosis. The shape and stiffness of the environment in which these cells grow play a significant role in their function. By using human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, researchers can study these effects in a controlled setting, replicating critical aspects of the heart environment outside the body.

Their study reveals that both the geometry of the cell space and the stiffness of the substrate impact how these cells generate force. When cells are confined in a specific space, they exhibit longer resting sarcomeres (the basic units of muscle contraction), more significant shortening of these sarcomeres, higher peak contractile stress, and faster mechanical relaxation.

These changes in behavior are more pronounced on substrates with physiological (10 kPa) stiffness compared to those with fibrotic (30 kPa) stiffness. On 10 kPa substrates, even though confinement doesn't alter the resting sarcomere length, it does enhance peak contractile stress and speeds up relaxation compared to unconfined cells.

At 30 kPa, these differences are less noticeable. Thus, both cell geometry and substrate stiffness are vital factors to consider when using hiPSC-derived cardiomyocytes for studying heart mechanics, modeling diseases, or testing drugs.