טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentHamrani Yael
SubjectCardiac Cell Beating on Matrices with Different Rigidities
DepartmentDepartment of Mechanical Engineering
Supervisor Professor Shelly Tzlil
Full Thesis textFull thesis text - English Version


Abstract

Cells sense the mechanical properties of their environment and respond to them. Extracellular matrix elasticity often provides a physical cues influencing cell shape, growth pattern and protein expression profile. Furthermore, environment elasticity is often altered in pathological situations. This includes the replacement of the normal cardiac cell environment by a scar tissue, several-fold stiffer than normal, after a myocardial infraction.

Here we study the beating pattern of cardiac cells on substrates with different rigidities. Substrate rigidity is controlled by either using a linear polymer gel or an engineered biomaterial substrate with tunable Young’s modulus.

We are able to corroborate the previous observations demonstrating optimal beating of cardiomyocytes at native tissue elasticity with reduced average beating frequency and increased average cell size for substrates with scar-tissue rigidity. In addition, we show that native tissue elasticity is correlated with optimal sarcomere fiber alignment.

On substrates with scar-tissue rigidity, the variability of cardiomyocyte spontaneous beating rate as well as the variability of cardiomyocyte size is much larger. In addition, on substrates with ‘scar-tissue-like’ rigidity, we observe cardiomyocytes with size that is 3-fold larger than the average size and spontaneous beating frequency that is 3-fold lower than the average beating frequency.

When the contractile machinery is inhibited, calcium oscillation frequency no longer depends on substrate mechanics.

A newly-designed sarcomeric-based-biomaterial was used in order to change substrate mechanics in real time and monitor cardiac cell beating both prior to the change in substrate mechanics and afterwards. Cardiomyocytes with abnormal early-afterdepolarization calcium oscillations cultured on sarcomeric-based-biomaterial were induced to beat regularly with a normal calcium signal within 30 minutes after reducing substrate rigidity.