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Statistical mechanical modeling of the effects of mechanical stretching on Intracellular Ca2+ concentration

Grant number: 19/16338-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2019
Effective date (End): July 31, 2023
Field of knowledge:Physical Sciences and Mathematics - Physics
Principal Investigator:Adriano Mesquita Alencar
Grantee:Yan Borges Barreto
Home Institution: Instituto de Física (IF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther, AP.TEM

Abstract

The objective of this project is to study the influence of mechanical stretching on Ca2+ transport across the cell membrane. To do this, we will develop a statistical mechanical model that provides the transmembrane Ca2+ flux as a function of the substrate stretching for two transport proteins, namely an ion channel, and the Na+/Ca2+ exchanger, NCX. This statistical mechanical model will be solved by the Monte Carlo method, which is a method with which our research group already has experience. The interest behind the modeling involving the ion channel lies in the fact that there is a large amount of experimental data on the effects of mechanical stretching on intracellular Ca2+ concentration. However, these data do not have a solid theoretical basis, since the existing models are not able to reproduce them satisfactorily. In the case of the NCX, the interest lies in the fact that, in experiments performed by our group, living cardiomyocyte cells regulated through a Ca2+ flux are adhered to a substrate that can be stretched to measure mechanical properties of such cells. These measurements are part of a FAPESP thematic project (2013/17368-0), whose aim is the regenaration of the heart. Thus, it is of fundamental importance to understand how the stretching of cardiomyocytes, among other cells, affects the Ca2+ transport by NCX. Our perpective is that the results of the present study may be used by the scientific community together with the experimental works that have been carried out to understand the effects of mechanical stimuli observed in vivo on the cell function.