Abstract:
The cytoskeleton is a complex network of interconnected biopolymers consisting of actin filaments, microtubules, and intermediate filaments. These biopolymers work in concert to transmit cell-generated forces to the extracellular matrix required for cell motility, wound healing, and tissue maintenance. While we know cell-generated forces are driven by actomyosin contractility and balanced by microtubule network resistance, the effect of intermediate filaments on cellular forces is unclear. Using a combination of theoretical modeling and experiments, we show that vimentin intermediate filaments tune cell stress by assisting in both actomyosin-based force transmission and reinforcement of microtubule networks under compression. We show that the competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. These results reconcile seemingly contradictory results in the literature and provide a unified description of vimentin\'s effects on the transmission of cell contractile forces to the extracellular matrix.
摘要:
细胞骨架是由肌动蛋白丝组成的相互连接的生物聚合物的复杂网络,微管,和中间长丝。这些生物聚合物协同工作,将细胞产生的力传递到细胞运动所需的细胞外基质,伤口愈合,和组织维护。虽然我们知道细胞产生的力是由肌动球蛋白收缩性驱动的,并由微管网络阻力平衡的,中间丝对细胞力的影响尚不清楚。采用理论建模和实验相结合的方法,我们表明,波形蛋白中间丝通过辅助基于肌动球蛋白的力传递和压缩下微管网络的增强来调节细胞应力。我们表明,波形蛋白的这两种相反作用之间的竞争受微环境刚度的调节。这些结果调和了文献中看似矛盾的结果,并提供了波形蛋白对细胞收缩力传递至细胞外基质的影响的统一描述。