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Heart Fi-Re: HEART FIne REgulation through mechanosensing in myosin filaments: merging theory and experiments into a multi-scale heart simulator
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Old posts will be published again soon. New posts will be sometime published in the meantime.
Attending conferences is an important part of the scientific research. It represent the the possibility to share information even before they reached definitive publishable results, to be updated about the most recent discoveries directly by the authors, to do networking and have informal discussions with people who do the same research as you, but differently, and last but not least... it push you to travel around the world! (Incidentally, from Osaka the shortest route is via the Hawaii, where I will stop by few days in the way back). As part of my project, I am going to San Diego (CA) to attend the Biophysical Society Annual Meeting, a five-day meeting with about 5,000 attendees, 500 speakers and 600 daily poster presentations, included mine. I will present an analysis about the calcium gradients in resting muscle cells generated by the leakage of the calcium-release channel. The channel (RyR) functionally opens during action potentials to release big a...
How important is the calcium diffusion in the sequential activation of the thick filament? I discussed about this topic in a previous post . With my collaborators at the Department of Biomedical Science s in Padova University, we are exploring this issue through a mathematical model based on experimental data on calcium signalling in the three main compartments of the muscle cells: sarcoplasmic reticulum, cytosol and mitoshondria. In fact, while usually neglected, we think that mithocondria may play an important role in the calcium distribution during activation, at least in skeletal muscle cells. Our work lead to an extensive review done with the priceless enormous contribution of Prof. Carlo Reggiani, just published in the Journal of General Physiology. You can read it here , but our main conclusion is that the mitochondria may have an important role, and that this must be elucidated with further analyses. From the point of view of the super relaxed state, and its activati...
The first part of my project aims at collecting as much as possible (AKA "all") the current knowledge of the mechanosensing mechanism, or WHY and HOW the super-relaxed myosin heads decide to rise up and start the actomyosin cycle to produce force. Here, I report a striking result from Brunello and Fusi, at King's College of London, published in PNAS in march 2020. The applied the X-ray diffraction technique to study the thick filament structure in cardiac muscle. Small angle XRay diffraction is one of the most used techniques to dynamically analyze the state of the thick filament, thanks to the different spacing that the myosin motors have in each state. The interpretation of the data is made through mathematical models of predicted X-ray diffractions from different populations. Despite it is necessarily based on some assumptions, its interpretation can be considered well established in the literature. I do not report here the beautiful pictures reported in the paper b...
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