Cultured vascular endothelial cells undergo significant morphological changes when subjected to sustained fluid shear stress. The cells elongate and align in the direction of applied flow. Accompanying this shape change is a reorganization at the intracellular level. The cytoskeletal actin filaments reorient in the direction of the cells' long axis. How this external stimulus is transmitted to the endothelial cytoskeleton still remains unclear. In this article, we present a theoretical model accounting for the cytoskeletal reorganization under the influence of fluid shear stress. We develop a system of integro-partial-differential equations describing the dynamics of actin filaments, the actin-binding proteins, and the drift of transmembrane proteins due to the fluid shear forces applied on the plasma membrane. Numerical simulations of the equations show that under certain conditions, initially randomly oriented cytoskeletal actin filaments reorient in structures parallel to the externally applied fluid shear forces. Thus, the model suggests a mechanism by which shear forces acting on the cell membrane can be transmitted to the entire cytoskeleton via molecular interactions alone.
The regulation of the interactions between the actin binding proteins and the actin filaments are known to affect the cytoskeletal structure of F-actin. We develop a model depicting the formation of actin cytoskeleton, bundles and orthogonal networks, via activation or inactivation of different types of actin binding proteins. It is found that as the actin filament density increases in the cell, a spontaneous tendency to organize into bundles or networks occurs depending on the active actin binding protein concentration. Also, a minute change in the relative binding affinity of the actin binding proteins in the cell may lead to a major change in the actin cytoskeleton. Both the linear stability analysis and the numerical results indicate that the structures formed are highly sensitive to changes in the parameters, in particular to changes in the parameter phi, denoting the relative binding affinity and concentration of the actin binding proteins.
EINLEITUNG: Die Übertragung von äußeren Kräften auf Endothelzellen führt zu signifikanten biochemischen und morphologischen Veränderungen [1]. Untersuchungen in-vivo und in-vitro demonstrieren im besonderen den Einfluß von fluß-induzierten Scherspannungen auf die Funktion und Erscheinungsform der Zellen [2]. Die Zellen verlängern und reorientieren sich in der Richtung der auf sie einwirkenden Blutströmung. Dieses Phänomen steht u.a. im Verdacht, in der Lokalisierung von arterioskeloritischen Plaques im Blutgefa'ßsystem involviert zu sein [3]. Die Änderung der äußeren morphologischen Form wird begleitet von einer Reorganisation des Zellskelettes im allgemeinen, und des F-Actin-Zytoskelettes im besonderen. Die einzelnen Actin-Filamente des grobmaschigen isotropen Netz-werkes, sowie vor allem die dominanten Actin-Stressfasern (siress fibers) reorientieren sich parallel zur langen Hauptachse der Zellen, und somit parallel zur Flußrichtung [4]. Die ursächlichen Mechanismen dieses Reorientierungsprozesses sind aber noch unklar und umstritten [5] und daher Gegenstand dieser Studie.
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