Department of Physics, Technische Universität München, 85748 Garching, Germany.
Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.
Sci Adv. 2016 Apr 15;2(4):e1500465. doi: 10.1126/sciadv.1500465. eCollection 2016 Apr.
Morphological transformations of living cells, such as shape adaptation to external stimuli, blebbing, invagination, or tethering, result from an intricate interplay between the plasma membrane and its underlying cytoskeleton, where molecular motors generate forces. Cellular complexity defies a clear identification of the competing processes that lead to such a rich phenomenology. In a synthetic biology approach, designing a cell-like model assembled from a minimal set of purified building blocks would allow the control of all relevant parameters. We reconstruct actomyosin vesicles in which the coupling of the cytoskeleton to the membrane, the topology of the cytoskeletal network, and the contractile activity can all be precisely controlled and tuned. We demonstrate that tension generation of an encapsulated active actomyosin network suffices for global shape transformation of cell-sized lipid vesicles, which are reminiscent of morphological adaptations in living cells. The observed polymorphism of our cell-like model, such as blebbing, tether extrusion, or faceted shapes, can be qualitatively explained by the protein concentration dependencies and a force balance, taking into account the membrane tension, the density of anchoring points between the membrane and the actin network, and the forces exerted by molecular motors in the actin network. The identification of the physical mechanisms for shape transformations of active cytoskeletal vesicles sets a conceptual and quantitative benchmark for the further exploration of the adaptation mechanisms of cells.
活细胞的形态转变,如对外界刺激的形状适应、起泡、内陷或系留,是由质膜与其下的细胞骨架之间的复杂相互作用引起的,其中分子马达产生力。细胞的复杂性使得难以明确识别导致这种丰富表型的竞争过程。在合成生物学方法中,设计由最小一组纯化构建块组装而成的类细胞模型将允许控制所有相关参数。我们重建肌动球蛋白囊泡,其中细胞骨架与膜的耦合、细胞骨架网络的拓扑结构和收缩活性都可以精确控制和调整。我们证明,封装的活性肌动球蛋白网络的张力产生足以引起细胞大小的脂质囊泡的整体形状转变,这类似于活细胞中的形态适应。我们的类细胞模型的观察到的多态性,如起泡、系留挤出或多面形状,可以通过蛋白浓度依赖性和力平衡来定性解释,考虑到膜张力、膜和肌动球蛋白网络之间的锚定点密度以及肌动球蛋白网络中分子马达施加的力。活性细胞骨架囊泡形状转变的物理机制的鉴定为进一步探索细胞适应机制提供了概念和定量基准。