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ES 240 Project: Stretching Cardiac Myocytes

Megan McCain's picture

In the ventricle of the heart, the cells (myocytes) are not isotropically arranged. Myocytes are cylindrically shaped and align edge to edge, and then form a large sheet of parallel rows of aligned cells. This "sheet" is wrapped around itself to form the thick wall of the heart. Myocytes are mechanically coupled to each other by desmosomes, and are electrically coupled to each other by connexins. These connections are extremely important in assuring the heart beats synchronously.

With advances in tissue engineering, it is possible to use fibronectin (an extracellular matrix protein that binds to the cell surface) to create essentially 2D monolayers of myocytes arranged in a striated pattern resembling that of the actual heart. Connexins and desmosomes will also form to link cells together, resembling in vivo tissue.

It is known that cells remodel themselves in response to stress, such as aligning parallel to the direction of a uniaxial stretch. Because hypertrophy and other cardiac conditions can subject myocytes to varying stress fields, myocytes and the proteins that couple them can be subjected to different stresses in pathological conditions and remodel in response. This can change their structural and therefore functional properties (such as conduction velocity), which can potentially lead to an arrhythmia.

For my project, I want to determine the stress field in a 2D monolayer of myocytes subjected to a uniaxial stretch, especially looking at how the stress field changes when the myocytes are aligned in different orientations relative to the direction of stretch (parallel, perpendicular, 45 degrees, etc). I want to model a 2D layer of myocytes that are coupled to each other end to end, but not side to side, and see how changing the orientation of the fibers relative to the direction of stress changes the amount of stresses seen at the sites of cellular connections. This would be important in understanding the remodeling process (especially of connexins) that occurs when the heart is subjected to different stress fields.

Attached are two papers further describing the effect of subjecting myocytes to stretch. These papers only describe the remodeling that happens in isotropic monolayers - no one has looked at the remodeling of striated monolayers (hopefully I will someday soon!).


I see a potential difficulty in using FEM for a tissue. In order to understand what stresses are present at connexins which are on the length scale of <10nm, you will need that sort of resolution of your material parameters, E and v and of your geometry. It seems that if you want 10nm resolution for σ you will also need 10nm resolution for E and v which will be very difficult to model since E(x,y,z,t) will be a very complicated field, same for v. I dont think you want to be bogged down creating such fields.

I would suggest staying away from connexins since this will require very tedious creation of the mesh geometry, and a very complex E and v field. But I think the idea of periodic stress on a tissue monolayer is very interesting. Perhaps you could look at stress distribution near heterogeneities, such as fibrotic or ischaemic tissue. The length scales of these objects will be sufficiently large so that the variations in E and v over the subcellular length scale will be smoothed over. I have read an interesting paper about stress and cardiac remodeling post myocardial infarction [ref below]. It may suggest some good ideas.

Holmes, Jerffrey et al. (he is the PI of the cardiac biophys lab at columbia). "Structure and Mechanics of Healing Myocardial Infarcts" Annu. Rev. Biomed. Eng. 2005. 7:223-253.

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