Probing The Generation Of Intracellular Active Mechanical Force

There are increasing reports on the key roles performed by the intracellular mechanical force in physiological process during recent years.Probing the generation of intracellular active mechanical force is not only essential to cell mechanics,but also of significance to physiology and biomedicine.Although there are numerous kinds of proteins and multitudinous underlying mechanisms involved in the force generation in cells,this thesis focuses on the two subcellular structures,sarcomere and stress fiber,both of which comprise actin and myosin.Combining finite element method with Monte Carlo method,the chemomechanical models of subcellular structures are established to investigate the mechanism of force generation in cells.The main contents of this thesis are listed below:(1)The sarcomere contractions under different adenosine triphosphate(ATP)concentration are simulated to investigate the effects of ATP concentration on sarcomere contraction.The relationship between ATP concentration and contractile velocity in simulation is in a remarkable consistency with experimental results.The force distribution on different states of molecular motor indicates that the molecular motors at rigor state resist contraction.When resistance is too high,the number of working motors fails to increase linearly with sarcomere load,and the force regulation of molecular motors becomes ineffective.High ATP concentration reduces resistance and makes the force on molecular motors regulated precisely.Simulations also suggest that the regular contraction of sarcomere needs the tensile stiffness of thin filament,EA,upon a certain value.(2)By simulating the interaction between cross linkers and two antiparallel filaments,the effects of physical and chemical parameters on the load history of the filaments are investigated.Simulation results suggest that high mechanical force can be either generated by the binding or unbinding polarity of passive linkers,suggesting a new way of generating intracellular active mechanical force.There could be a catastrophic instability during the load process of binding polarity.The instability might be helpful to the quick response to changes in extracellular environment.