The MechChem model of sarcomere contraction
Tammo Delhaas
Chair of Biomedical Engineering at Maastricht University
DEIB - Building 21, Alario Room (first floor, Via Golgi n. 39, Milano)
September 21st, 2016
3.00 pm
Contact:
Enrico Caiani
Research Line:
Physiological modeling, diagnostics, health systems and e-health
Chair of Biomedical Engineering at Maastricht University
DEIB - Building 21, Alario Room (first floor, Via Golgi n. 39, Milano)
September 21st, 2016
3.00 pm
Contact:
Enrico Caiani
Research Line:
Physiological modeling, diagnostics, health systems and e-health
Sommario
We developed a model of cardiac sarcomere contraction to study the calcium-tension relationship in cardiac muscle. Calcium mediates cardiac contraction through its interactions with troponin (Tn) and subsequently tropomyosin molecules. Experimental studies have shown that a slight increase in intracellular calcium concentration leads to a rapid increase in sarcomeric tension. Though it is widely accepted that the rapid increase is not possible without the concept of cooperativity, the mechanism is debated. We use the hypothesis that there exists a base level of cooperativity intrinsic to the thin filament that is boosted by mechanical tension, i.e. a high level of mechanical tension in the thin filament impedes the unbinding of calcium from Tn. To test these hypotheses, we developed a computational model in which a set of three parameters and inputs of calcium concentration and sarcomere length result in output tension. Tension as simulated appeared in good agreement with experimentally measured tension. Our results support the hypothesis that high tension in the thin filament impedes Tn deactivation by increasing the energy required to detach calcium from the Tn. Given this hypothesis, the model predicted that the areas with highest tension, i.e. closest to the Z-disk end of the single overlap region, show the largest concentration of active Tn’s.
Biografia
Tammo Delhaas obtained his MD at the University of Groningen. He received his PhD degree from Maastricht University for a thesis on cardiac mechanics. After his training in Pediatrics in Maastricht and Utrecht, he spend one year at the Departments of Bioengineering and Medicine from the UCSD on a Fulbright grant / ICIN-Fellowship. Thereafter he trained in Pediatric Cardiology in Aachen and Melbourne. In 2009 he was appointed professor and chair of Biomedical Engineering at Maastricht University. With clinical questions regarding (congenital) heart diseases in mind, his research focuses on the following subjects: vascular and myocardial structure-function relation, myocardial adaptation, asynchronous myocardial electrical activation, and computer model assisted diagnosis and treatment of vascular access, cardiac failure, pulmonary hypertension and congenital heart diseases. He has authored over 145 papers and organized several international conferences on modeling in cardiovascular research. He received generous funding from, amongst others, the Dutch Heart Foundation, the Interuniversity Cardiology Institute of Netherlands (Royal Dutch Academy of Sciences), the Dutch Organization for Fundamental Research, the Dutch Kidney Foundation, and the Province of Limburg.