Local tissue mechanics control cardiac pacemaker cell embryonic patterning

Abstract

Cardiac pacemaker cells (CPCs) initiate the electric impulses that drive the rhythmic beating of the heart. CPCs reside in a heterogeneous, ECM-rich microenvironment termed the sinoatrial node (SAN). Surprisingly, little is known regarding the biochemical composition or mechanical properties of the SAN, and how the unique structural characteristics present in this region of the heart influence CPC function remains poorly understood. Here, we have identified that SAN development involves the construction of a “soft” macromolecular ECM that specifically encapsulates CPCs. In addition, we demonstrate that subjecting embryonic CPCs to substrate stiffnesses higher than those measured in vivo results in loss of coherent electrical oscillation and dysregulation of the HCN4 and NCX1 ion channels required for CPC automaticity. Collectively, these data indicate that local mechanics play a critical role in maintaining the embryonic CPC function while also quantitatively defining the range of material properties that are optimal for embryonic CPC maturation.

Omental coating attenuates implant-induced foreign body reaction in rats

“…Materials and devices implanted in the body, such as glucose sensors, 1 breast implants, 2,3 cardiac pacemaker, 4,5 or brain pacemaker, [6][7][8] have been used for tissue replacement and reconstruction, drug delivery, biosensors and so on. [9][10][11] Though offering remarkable clinical benefits, the body's immune system recognizes such implants as foreign, and result in persistent inflammatory reaction called the foreign body reaction (FBR), often lead to tissue distortion, pain, and chronic wounds.…”