|Tseng, Yiider - JOHNS HOPKINS UNIV|
|Wirtz, Denis - JOHNS HOPKINS UNIV|
Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 22, 2000
Publication Date: N/A
Interpretive Summary: Cell movement and cell shape control are related with cell division, organ development, muscle contraction, cancer development, etc. People have been known that cell migration and shape depend on mechanical properties of a network of protein filaments that extends throughout the cytoplasm which is a organized complex of inorganic and organic substances external to the nuclear membrane of a cell. This network of protein filaments is called cytoskeleton. However, the mechanisms by which extracellular and intracellular mechanical stresses regulate the cytoskeleton organization are not well understood. This work studied mechanical properties of actin filament networks, a major protein component of the cytoskeleton, as well as actin filament with crosslinking protein alpha-actinin. We find that actin filament network exhibits slight strain-hardening, i.e. the elasticity increases with its deformation. In addition, crosslinking protein a-actinin dramatically enhances this trend. We propose a simple model to explain the origin of strain-hardening of actin filament network with and without crosslinking. This model provides a molecular basis for explaining the origin of strain-hardening detected in vivo when the cytoskeleton is subject to mechanical stresses. This work is important to the scientists and medical doctors in cell biology, cancer research, organ development, pharmaceutical research, etc. in that this research gave an explanation of cells response to the external stresses.
Technical Abstract: Mechanical stresses applied to the plasma membrane of an adherent cell induces strain-hardening of the cytoskeleton, i.e. the elasticity of the cytoskeleton increases with its deformation. Strain-hardening is thought to promote the transduction of mechanical signals across the plasma membrane through the cytoskeleton, to the nucleus. Here, we describe the mechanical response of a model system consisting of actin filaments and the F-actin crosslinking protein alpha-actinin. We show that the presence of alpha-actinin greatly enhances the mechanical response of F-actin networks subject to shear deformations. At low temperatures, for which the lifetime of binding of alpha-actinin to F-actin is long, F-actin/a-actinin networks exhibit strong strain-hardening at short times scales and soften at long time scales. The modulus of a crosslinked network under strain increases between 20 and 250%, depending on time scale, compared to the modulus at small deformations. For F-actin networks in the absence of a-actinin or for F-actin/a-actinin networks at high temperatures, strain-hardening appears only at very short time scales. The rate at which a crosslinked F-actin network softens under large deformations decreases steeply with temperature. We propose a model of strain-hardening for F-actin networks, based on both the intrinsic rigidity of actin filaments and topological constraints formed by dynamic entanglements in a crosslinked F-actin network. This model offers an explanation for the origin of strain-hardening observed when shear stresses are applied against plasma membrane.