A Computational Model for Cardiomyocytes Mechano-Electric Stimulation to Enhance Cardiac Tissue Regeneration

Abstract

Electrical and mechanical stimulations play a key role in cell biological processes, being essential in processes such as cardiac cell maturation, proliferation, migration, alignment, attachment, and organization of the contractile machinery. However, the mechanisms that trigger these processes are still elusive. The coupling of mechanical and electrical stimuli makes it difficult to abstract conclusions. In this sense, computational models can establish parametric assays with a low economic and time cost to determine the optimal conditions of in-vitro experiments. Here, a computational model has been developed, using the finite element method, to study cardiac cell maturation, proliferation, migration, alignment, and organization in 3D matrices, under mechano-electric stimulation. Different types of electric fields (continuous, pulsating, and alternating) in an intensity range of 50–350 Vm−1, and extracellular matrix with stiffnesses in the range of 10–40 kPa, are studied. In these experiments, the group’s morphology and cell orientation are compared to define the best conditions for cell culture. The obtained results are qualitatively consistent with the bibliography. The electric field orientates the cells and stimulates the formation of elongated groups. Group lengthening is observed when applying higher electric fields in lower stiffness extracellular matrix. Groups with higher aspect ratios can be obtained by electrical stimulation, with better results for alternating electric fields.

Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model

“…It has been seen that it improves cell maturation, contractile capacities, and alignment [ 16 , 17 , 54 , 66 ]. Although the effects of the mechanical and electrical stimulation can be beneficial, the study of the cellular response due to their coupling effect is not straightforward [ 40 ]. Thus, here, we studied the coupling of these effects on CMs behavior.…”

“…As the mechanical and electrical stimuli are considered in the present model, cell polarization can be defined by [ 39 ] where and are the direction of the mechanical and electrical stimuli, respectively. Thus, mechanical stimuli direction, , can be calculated as [ 49 , 50 ] and the electrical stimuli direction can be calculated as [ 40 , 49 ] …”

“…These models can thoroughly consider cell–cell and cell–ECM interactions, as well as the local influence of the different stimuli on cells. Among these models, different approaches can be found in cell migration [ 30 , 31 , 32 , 33 , 34 ], morphology [ 35 , 36 , 37 , 38 ], proliferation [ 39 , 40 ], and differentiation [ 41 , 42 ]. However, neither the collective behavior resulting from cardiomyocyte (CM) intercommunication nor the formation of stable cell adhesions has been considered before.…”

Finite Element Model for Cardiac Cell mechano-electrical stimulation

“…These forces include traction forces, , due to the contraction of the Actin-Myosin machinery, protrusion forces, , due to the random generation of cell protrusions, electric forces, , due to the electrostatic effect, and drag forces, , due to the movement on a viscous ECM. Thus, the force balance is defined as [7,8]:…”

“…This coupling of different stimulus makes it difficult to establish the required optimum cell culture conditions, which requires an elevated number of experimental assays. In this way, computational models can dramatically reduce the number of in-vitro experiments to establish the adequate conditions [5][6][7].…”