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ES 240 project: Deformation of the Sarcolemma

The cardiac myocyte is the basic contractile unit of the heart. In addition to potentiating contraction through chemical and electrical means, each myocyte is a complex sensor that monitors the mechanics of the heart. Through largely unknown means, mechanical stimuli are transduced into biochemical information and responses. Such mechanotransduction has been implicated in the etiology of many cardiovascular pathologies [1]. One such mechanical parameter that the myocyte most likely monitors is the hydrostatic pressure in the myocardium.

I would like to investigate one potential sensing mechanism. The myocyte contains myofibrils which are the molecular players responsible for contraction (http://en.wikipedia.org/wiki/Myofibril). These run the length of the myocyte (which is roughly a cylinder) and are tethered into the sarcolemma (the cell membrane of the myocyte). The sarcolemma is an elastic surface able to be deformed by hydrostatic pressure from the interior and exterior of the cell as well as by the myofibrils which pull on the membrane in a periodic manner. I would like to use finite element modeling to understand the displacement field of the sarcolemma under different hydrostatic conditions. I believe this is important since the displacement of the sarcolemma will be coupled to the strain of the myofibrils which many believe to a mechanism of mechanotransduction into biochemical signals.

 

1: Hoshijima, Masahiko. Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures. Am. J. Physiol. Heart Circ Physiol. 290: 1313-1325, 2006. 

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Comments

Megan McCain's picture

It would be interesting to apply your model to the different phases of the cardiac cycle, such as the start of diastole, when the sarcolemma would be exposed to positive pressure inside the cell at the points of myofibril attachment (due to titin acting as a spring) and a global negative pressure outside the cell. You could also relate your model to the hypothesis that the ventricle acts as a suction pump during diastole due to the presence of negative hydrostatic pressures (see reference). The reference I listed discusses the suction pump hypothesis, as well as providing values for pressures inside the ventricle during different phases of the cardiac cycle.

Buckberg, et al. Active myocyte shortening during the 'isovolumetric relaxation' phase of diastole is responsible for ventricular suction; 'systolic ventricular filling.' European Journal of Cardio-thoracic Surgery 29S (2006) S98-S106.

I have posted 3 papers relevant to your project (see my blog).  I will briefly discuss what I think are some important insights they offer for your project.

As you mentioned in your comment on Megan's project, choosing a simple representation of the load-bearing structures in a cell or tissue is a critical and difficult task.  One of the papers I've posted discusses two possibilities: 1) Modelling a cell with uniform, "averaged" mechanical properties and 2) Modelling a cell with wire-like myofibrils and other structural elements, homogeneous and very pliable other than the chosen structural elements.  In the first method, the cell can be given anisotropic material properties, as one observes in the lab.

The Circulation paper discusses the difference in observed response to the same stimulus, pressure, when applied during systole and diastole.  It mights be interesting to try to answer in a heuristic way the following question in your project: given what is known about the different mechanical properties of cardiac myocytes in systole and diastole, which aspects of the difference in a cell's mechanical response to hydrostatic pressure might result in differently tranduced signals?  For example, does the same change in hydrostatic pressure in systole and diastole produce different stresses in myofibrils?

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